Updated on 2022/03/30

写真a

 
MIZOGUCHI, Hiroyuki
 
Organization
Nagoya University Hospital Department of Hospital Pharmacy Associate professor
Graduate School
Graduate School of Medicine
Title
Associate professor
Contact information
メールアドレス

Degree 2

  1. 博士(医学) ( 2005.3   名古屋大学 ) 

  2. 修士(薬学) ( 2001.3   京都薬科大学 ) 

Research Interests 2

  1. Neuropsychopharmacology

  2. Neuropsychopharmacology

Research Areas 2

  1. Life Science / Basic brain sciences

  2. Life Science / Basic brain sciences

Current Research Project and SDGs 5

  1. アルツハイマー病モデルマウスにおける認知記憶障害の発症機序の解明

  2. 覚せい剤精神病および統合失調症の発症機序の解明

  3. 薬物依存の形成機序の解明

  4. やる気の機序解明

  5. 意思決定・リスク志向な脳内神経回路の解明とその異常

Research History 9

  1. Nagoya University   Nagoya University Hospital Department of Hospital Pharmacy   Associate professor

    2020.8

  2. Nagoya University   Research Institute of Environmental Medicine Research Center for Next-Generation Drug Development   Lecturer

    2016.7 - 2020.7

  3. Nagoya University   Research Institute of Environmental Medicine Research Center for Next-Generation Drug Development   Assistant Professor

    2015.4 - 2016.6

  4. Nagoya University   Research Institute of Environmental Medicine Futuristic Environmental Simulation Center   Assistant Professor

    2007.7 - 2015.3

  5. 名古屋大学環境医学研究所附属近未来環境シミュレーションセンター 助教

    2007.7

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    Country:Japan

  6. Nagoya University   Research Institute of Environmental Medicine

    2007.7

  7. 金沢大学大学院自然科学研究科薬物治療学研究室助教

    2007.4 - 2007.6

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    Country:Japan

  8. 金沢大学大学院自然科学研究科薬物治療学研究室助手

    2006.4 - 2007.3

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    Country:Japan

  9. 名古屋大学大学院医学系研究科研究員

    2005.4 - 2006.3

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    Country:Japan

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Education 3

  1. Nagoya University   Graduate School, Division of Medical Sciences

    2001.4 - 2005.3

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    Country: Japan

  2. Kyoto Pharmaceutical University   Graduate School, Division of Pharmaceutical Sciences

    1999.4 - 2001.3

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    Country: Japan

  3. Kyoto Pharmaceutical University   Faculty of Pharmaceutical Science

    1995.4 - 1999.3

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    Country: Japan

Professional Memberships 14

  1. Society for Neuroscience

  2. 日本神経化学会

  3. 日本神経科学会

  4. 日本生物学的精神医学会

  5. 日本神経精神薬理学会

  6. 日本薬学会

  7. 日本薬理学会

  8. 日本薬理学会

  9. 日本薬学会

  10. 日本神経精神薬理学会

  11. 日本神経科学会

  12. 日本神経化学会

  13. 日本生物学的精神医学会

  14. Society for Neuroscience

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Awards 3

  1. 第6回アジア神経精神薬理学会Outstanding Research Award for AsCNP2019

    2019   AsCNP2019  

  2. 日本アルコール・アディクション医学会 柳田知司賞

    2018   日本アルコール・アディクション医学会  

  3. 日本神経精神薬理学会学術奨励賞

    2018   日本神経精神薬理学会  

 

Papers 116

  1. A machine learning model that emulates experts' decision making in vancomycin initial dose planning. Reviewed

    Matsuzaki T, Kato Y, Mizoguchi H, Yamada K

    Journal of pharmacological sciences   Vol. 148 ( 4 ) page: 358 - 363   2022.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Pharmacological Sciences  

    Vancomycin is a glycopeptide antibiotic that is a primary treatment for methicillin-resistant Staphylococcus aureus infections. To enhance its clinical effectiveness and prevent nephrotoxicity, therapeutic drug monitoring (TDM) of trough concentrations is recommended. Initial vancomycin dosing regimens are determined based on patient characteristics such as age, body weight, and renal function, and dosing strategies to achieve therapeutic concentration windows at initial TDM have been extensively studied. Although numerous dosing nomograms for specific populations have been developed, no comprehensive strategy exists for individually tailoring initial dosing regimens; therefore, decision making regarding initial dosing largely depends on each clinician's experience and expertise. In this study, we applied a machine-learning (ML) approach to integrate clinician knowledge into a predictive model for initial vancomycin dosing. A dataset of vancomycin initial dose plans defined by pharmacists experienced in vancomycin TDM (i.e., experts) was used to build the ML model. Although small training sets were used, we established a predictive model with a target attainment rate comparable to those of experts, another ML model, and commonly used vancomycin dosing software. Our strategy will help develop an expert-like predictive model that aids in decision making for initial vancomycin dosing, particularly in settings where dose planning consultations are unavailable.

    DOI: 10.1016/j.jphs.2022.02.005

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  2. New Strategies for the Treatment of Neuropsychiatric Disorders Based on Reelin Dysfunction Reviewed

    Tsuneura Yumi, Nakai Tsuyoshi, Mizoguchi Hiroyuki, Yamada Kiyofumi

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 23 ( 3 )   2022.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:International Journal of Molecular Sciences  

    Reelin is an extracellular matrix protein that is mainly produced in Cajal-Retzius cells and controls neuronal migration, which is important for the proper formation of cortical layers in the developmental stage of the brain. In the adult brain, Reelin plays a crucial role in the regulation of N-methyl-D-aspartate receptor-dependent synaptic function, and its expression decreases postnatally. Clinical studies showed reductions in Reelin protein and mRNA expression levels in patients with psychiatric disorders; however, the causal relationship remains unclear. Reelin-deficient mice exhibit an abnormal neuronal morphology and behavior, while Reelin supplementation ameliorates learning deficits, synaptic dysfunctions, and spine loss in animal models with Reelin deficiency. These findings suggest that the neuronal deficits and brain dysfunctions associated with the down-regulated expression of Reelin are attenuated by enhancements in its expression and functions in the brain. In this review, we summarize findings on the role of Reelin in neuropsychiatric disorders and discuss potential therapeutic approaches for neuropsychiatric disorders associated with Reelin dysfunctions.

    DOI: 10.3390/ijms23031829

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  3. Mice with exonic RELN deletion identified from a patient with schizophrenia have impaired visual discrimination learning and reversal learning in touchscreen operant tasks Reviewed

    Liao Jingzhu, Dong Geyao, Wulaer Bolati, Sawahata Masahito, Mizoguchi Hiroyuki, Mori Daisuke, Ozaki Norio, Nabeshima Toshitaka, Nagai Taku, Yamada Kiyofumi

    BEHAVIOURAL BRAIN RESEARCH   Vol. 416   page: 113569   2022.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Behavioural brain research  

    The Reelin gene (RELN) encodes a large extracellular protein, which has multiple roles in brain development and adult brain function. It activates a series of neuronal signal transduction pathways in the adult brain that function in synaptic plasticity, dendritic morphology, and cognitive function. To further investigate the roles of Reln in brain function, we generated a mouse line using the C57BL/6 J strain with the specific Reln deletion identified from a Japanese patient with schizophrenia (Reln-del mice). These mice exhibited abnormal sociality, but the pathophysiological significance of the Reln deletion for higher brain functions, such as learning and behavioral flexibility remains unclear. In this study, cognitive function in Reln-del mice was assessed using touchscreen-based visual discrimination (VD) and reversal learning (RL) tasks. Reln-del mice showed normal learning in the simple VD task, but the learning was delayed in the complex VD task as compared to their wild-type (WT) littermates. In the RL task, sessions were divided into early perseverative phase (sessions with <50% correct) and later learning phase (sessions with ≥50% correct). Reln-del mice showed normal perseveration but impaired relearning ability in both simple RL and complex RL task as compared to WT mice. These results suggest that Reln-del mice have impaired learning ability, but the behavioral flexibility is unaffected. Overall, the observed behavioral abnormalities in Reln-del mice suggest that this mouse model is a useful preclinical tool for investigating the neurobiological mechanism underlying cognitive impairments in schizophrenia and a therapeutic strategy.

    DOI: 10.1016/j.bbr.2021.113569

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  4. Alzheimer's Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment Reviewed

    Nakai Tsuyoshi, Yamada Kiyofumi, Mizoguchi Hiroyuki

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 22 ( 11 )   2021.6

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:International Journal of Molecular Sciences  

    Alzheimer’s disease (AD) is an age-related and progressive neurodegenerative disorder. It is widely accepted that AD is mainly caused by the accumulation of extracellular amyloid β (Aβ) and intracellular neurofibrillary tau tangles. Aβ begins to accumulate years before the onset of cognitive impairment, suggesting that the benefit of currently available interventions would be greater if they were initiated in the early phases of AD. To understand the mechanisms of AD pathogenesis, various transgenic mouse models with an accelerated accumulation of Aβ and tau tangles have been developed. However, none of these models exhibit all pathologies present in human AD. To overcome these undesirable phenotypes, APP knock-in mice, which were presented with touchscreen-based tasks, were developed to better evaluate the efficacy of candidate therapeutics in mouse models of early-stage AD. This review assesses several AD mouse models from the aspect of biomarkers and cognitive impairment and discusses their potential as tools to provide novel AD therapeutic approaches.

    DOI: 10.3390/ijms22115549

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  5. Analysis of Reelin signaling and neurodevelopmental trajectory in primary cultured cortical neurons with RELN deletion identified in schizophrenia Reviewed

    Tsuneura Yumi, Sawahata Masahito, Itoh Norimichi, Miyajima Ryoya, Mori Daisuke, Kohno Takao, Hattori Mitsuharu, Sobue Akira, Nagai Taku, Mizoguchi Hiroyuki, Nabeshima Toshitaka, Ozaki Norio, Yamada Kiyofumi

    NEUROCHEMISTRY INTERNATIONAL   Vol. 144   page: 104954   2021.3

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Neurochemistry International  

    Reelin, an extracellular matrix protein, is secreted by Cajal-Retzius cells and plays crucial roles in the development of brain structures and neuronal functions. Reductions in Reelin cause the brain dysfunctions associated with mental disorders, such as schizophrenia. A recent genome-wide copy number variation analysis of Japanese schizophrenia patients identified a novel deletion in RELN encoding Reelin. To clarify the pathophysiological role of the RELN deletion, we developed transgenic mice carrying the RELN deletion (Reln-del) and found abnormalities in their brain structures and social behavior. In the present study, we performed an in vitro analysis of Reelin expression, intracellular Reelin signaling, and the morphology of primary cultured cortical neurons from wild-type (WT) and Reln-del mice. Reelin protein levels were lower in Reln-del neurons than in WT neurons. Dab1 expression levels were significantly higher in Reln-del neurons than in WT neurons, suggesting that Reelin signaling was decreased in Reln-del neurons. Reelin was mainly expressed in γ-aminobutyric acid (GABA)-ergic inhibitory neurons, but not in parvalbumin (PV)-positive neurons. A small proportion of Ca2+/calmodulin-dependent protein kinase II α subunit (CaMKIIα)-positive excitatory neurons also expressed Reelin. In comparisons with WT neurons, significant decreases were observed in neurite lengths and branch points as well as in the number of postsynaptic density protein 95 (PSD95) immunoreactive puncta in Reln-del neurons. A disintegrin and metalloproteinase with thrombospondin motifs-3 (ADAMTS-3) is a protease that inactivates Reelin by cleavage at the N-t site. The knockdown of ADAMTS-3 by short hairpin RNAs suppressed Reelin cleavage in conditioned medium and reduced Dab1 expression, indicating that Reelin signaling was enhanced in the primary cultured cortical neurons of WT and heterozygous Reln-del. Accordingly, the inhibition of ADAMTS-3 may be a potential candidate in the clinical treatment of schizophrenia by enhancing Reelin signaling in the brain.

    DOI: 10.1016/j.neuint.2020.104954

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  6. REM sleep-active MCH neurons are involved in forgetting hippocampus-dependent memories Reviewed

    Izawa Shuntaro, Chowdhury Srikanta, Miyazaki Toh, Mukai Yasutaka, Ono Daisuke, Inoue Ryo, Ohmura Yu, Mizoguchi Hiroyuki, Kimura Kazuhiro, Yoshioka Mitsuhiro, Terao Akira, Kilduff Thomas S., Yamanaka Akihiro

    SCIENCE   Vol. 365 ( 6459 ) page: 1308 - +   2019.9

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Science  

    The neural mechanisms underlying memory regulation during sleep are not yet fully understood.We found that melanin concentrating hormone-producing neurons (MCH neurons) in the hypothalamus actively contribute to forgetting in rapid eye movement (REM) sleep. Hypothalamic MCH neurons densely innervated the dorsal hippocampus. Activation or inhibition of MCH neurons impaired or improved hippocampus-dependent memory, respectively. Activation of MCH nerve terminals in vitro reduced firing of hippocampal pyramidal neurons by increasing inhibitory inputs.Wake- and REM sleep- active MCH neurons were distinct populations that were randomly distributed in the hypothalamus. REM sleep state-dependent inhibition of MCH neurons impaired hippocampus-dependent memory without affecting sleep architecture or quality. REM sleep-active MCH neurons in the hypothalamus are thus involved in active forgetting in the hippocampus.

    DOI: 10.1126/science.aax9238

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  7. Preproenkephalin-expressing ventral pallidal neurons control inhibitory avoidance learning Reviewed

    Macpherson Tom, Mizoguchi Hiroyuki, Yamanaka Akihiro, Hikida Takatoshi

    NEUROCHEMISTRY INTERNATIONAL   Vol. 126   page: 11 - 18   2019.6

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Neurochemistry International  

    The ventral pallidum (VP) is a critical component of the basal ganglia neurocircuitry regulating learning and decision making; however, its precise role in controlling associative learning of environmental stimuli conditioned to appetitive or aversive outcomes is still unclear. Here, we investigated the expression of preproenkephalin, a polypeptide hormone previously shown to be expressed in nucleus accumbens neurons controlling aversive learning, within GABAergic and glutamatergic VP neurons. Next, we explored the behavioral consequences of chemicogenetic inhibition or excitation of preproenkephalin-expressing VP neurons on associative learning of reward- or aversion-paired stimuli in autoshaping and inhibitory avoidance tasks, respectively. We reveal for the first time that preproenkephalin is expressed predominantly in GABAergic rather than glutamatergic VP neurons, and that excitation of these preproenkephalin-expressing VP neurons was sufficient to impair inhibitory avoidance learning. These findings indicate the necessity for inhibition of preproenkephalin-expressing VP neurons for avoidance learning, and suggest these neurons as a potential therapeutic target for psychiatric disorders associated with maladaptive aversive learning.

    DOI: 10.1016/j.neuint.2019.02.011

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  8. Maternal separation as a risk factor for aggravation of neuropathic pain in later life in mice

    Hiroyuki Mizoguchi, Kazuya Fukumoto, Gaku Sakamoto, Shijie Jin, Asako Toyama, Tian Wang, Akio Suzumura, Jun Sato

    Behavioural Brain Research   Vol. 359   page: 942 - 949   2019.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier B.V.  

    Psychological stresses such as social loss and separation during childhood induce hardship, referred to as emotional pain. These experiences are well-documented risk factors for the development of physical pain in adulthood. However, the underlying neuronal mechanisms of this exacerbation of pain are largely unknown, and consequently there is no effective pharmacotherapy. In this study, we sought to determine whether infant maternal separation (MS) contributes to aggravation of neuropathic pain in adult mice. MS increased anxiety- and depression-like behavioral responses to adult stress. In MS animals, chronic constriction injury (CCI) heightened the sensory dimension of chronic pain relative to that of control mice. However, MS mice treated with fluoxetine for 4 weeks after MS did not exhibit augmentation of allodynia, and their emotional response was attenuated. Microglia were more abundant in the spinal cord in MS/CCI mice than in control/CCI mice. These results suggest that emotional impairment is related to augmentation of neuropathic pain, and that dysfunction of microglial activation contributes to heightened pain sensitivity.

    DOI: 10.1016/j.bbr.2018.06.015

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  9. Nicotine and varenicline ameliorate changes in reward-based choice strategy and altered decision-making in methamphetamine-treated rats

    Hiroyuki Mizoguchi, Tian Wang, Mizuki Kusaba, Kazuya Fukumoto, Kiyofumi Yamada

    Behavioural Brain Research   Vol. 359   page: 935 - 941   2019.2

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    Patients suffering from neuropsychiatric disorders such as substance use and addiction disorders show impaired decision-making, which may be associated with their psychiatric disorders. Previously, using a gambling test for rodents, we demonstrated that methamphetamine-dependent rats showed alterations in their decision-making strategy. In this study, we investigated the effect of nicotine on impaired decision-making strategy in rats which have been treated repeatedly with methamphetamine. Nicotine has previously been shown to have therapeutic effects on attentional and cognitive abnormalities in psychosis. Rats were administered methamphetamine subcutaneously (sc) at 4 mg/kg once a day, for 30 days, and their decision-making was then assessed with a rodent gambling task. We found that methamphetamine-treated rats preferred the high-risk/high-return actions, which is consistent with our previous findings. Methamphetamine-induced impairment of decision-making was reversed by daily nicotine treatment (0.3 mg/kg, sc). This effect was associated with the reduction of lose-shift behavior after negative reward prediction error. Repeated treatment with nicotine had no effects on arm-choice behavior in naïve rats. Varenicline, an α4β2-nicotinic acetylcholine receptor partial agonist, also ameliorated the altered decision-making in methamphetamine-treated rats. Our findings suggest that nicotine treatment is useful for ameliorating the altered decision-making caused by methamphetamine treatment, and that the α4β2-nicotinic acetylcholine receptor is a therapeutic target for poor decision-making.

    DOI: 10.1016/j.bbr.2018.06.016

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  10. Physiological centers of decision-making: manipulation of neural activity in insular cortex by AAV

    Mizoguchi Hiroyuki, Yamada Kiyofumi

    Folia Pharmacologica Japonica   Vol. 153 ( 5 ) page: 224 - 230   2019

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    Language:Japanese   Publisher:The Japanese Pharmacological Society  

    <p>Decision-making is a key activity process that influences many aspects of daily living and both mental and physical health. In general, healthy participants reveal rational choice, but patients with neuropsychiatric disorders reveal irrational and risky choice in decision-making. Addiction is one of typical diseases revealed risky decision-making, addicts select risky action and options that confer short-term rewards at the cost of long-term disadvantages. Thus, irrational and risky decision-making is recognized as a core problem in patients with neuropsychiatric disorders, and a better understanding of the mechanisms underlying altered decision-making would provide insights into potential therapeutic approaches for these diseases. However, the neural pathway and substrates underlying these deficits are particularly unknown. Recently, we found that insular cortex is one of key regions for risky decision-making in an animal model of methamphetamine addiction, by using the designer receptor exclusively activated by designer drug (DREADD) technology, and that GABAergic dysfunction in insular cortex is involved in evaluating the subjective value of reward and reward prediction error. These brain dysfunctions would be related to risk taking behavior in addiction. In this review, we introduced the possible neural pathway related to risky decision-making and behavioral changes in choice strategy using adeno associated virus (AAV).</p>

    DOI: 10.1254/fpj.153.224

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  11. Behavioral characterization of APP knock-in mice model in touchscreen-based tests aiming early detection of Alzheimer's disease.

    Saifullah MD. Ali Bin, Komine Okiru, Sobue Akira, Yamanaka Koji, Mizoguchi Hiroyuki

    Proceedings for Annual Meeting of The Japanese Pharmacological Society   Vol. 92 ( 0 ) page: 1-P-041 - P-041   2019

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    Language:Japanese   Publisher:Japanese Pharmacological Society  

    <p>Alzheimer's disease (AD) is a progressive disease characterized by loss of memory and other important mental functions. Accumulation of amyloid beta (Aβ) and fibrillary tangles are the main pathological hallmarks of this disease. Emerging data suggest that the disease process begins years before clinical diagnostic confirmation; thus, methods to improve early detection would provide opportunities for early intervention to delay progressive cognitive decline and disease onset. In our research we assessed the cognitive abilities of <i>APP</i><sup><i>NL-G-F/NL-G-F</i></sup> knock-in (<i>APP-</i>KI) mice with a touch screen-based automated test battery and water maze test. These tests are mainly dependent on the brain regions that are prone to Aβ accumulation at the earliest stages of the disease. We subjected male 6- and 11-months old <i>APP-</i>KI mice in water maze test where only older mice showed significantly worsened behavior than wild-type mice. However, using touchscreen based behavioral test it was possible to detect cognitive impairment in <i>APP-</i>KI mice at an early (4 months) stage while classical behavioral tests shows comparable results between wild-type and disease model mice. </p>

    DOI: 10.1254/jpssuppl.92.0_1-p-041

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  12. Optimization of operant test for testing risky decision-making in mice

    Mizoguchi Hiroyuki, Wang Tian, Saifullah Md. Ali Bin, Fukumoto Kazuya, Yamada Kiyofumi

    Proceedings for Annual Meeting of The Japanese Pharmacological Society   Vol. 92 ( 0 ) page: 1-P-023 - P-023   2019

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    Language:Japanese   Publisher:Japanese Pharmacological Society  

    <p>Decision making in complex and uncertain situations is a fundamental adaptive process resulting from the integration of several executive functions. Impaired decision-making is a symptomatic feature of a number of psychiatric disorders. In general, patients with psychiatric disorders show a propensity to prefer actions associated with large short-term gains but long-term losses preferentially to those associated with small but long-term gains. They are more likely to select risky options and show an altered temporal horizon of risks and benefits. Moreover, clinical studies report that dopamine therapy induce impaired decision-making in patients with dopaminergic dysfunction such as Parkinson's disease and Redox-less syndrome. Thus, to establish and optimize the animal model of impaired decision-making is important for development of new therapeutic strategy in these disorders.</p><p>To clarify the underlying neurobiology of decision-making, we conducted a study in healthy mice by using a mouse gambling operant test based on uncertainty and conflicting choices. Mice chose the low-risk / low-reward option on the reward amount- and provability-dependent manner. Our findings suggest that healthy mice prefer risk-aversive choice in this operant test as dose man in Iowa gambling test.</p>

    DOI: 10.1254/jpssuppl.92.0_1-p-023

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  13. Basic researches to support the symbiotic society with dementia

    Yanai Shuichi, Takase Kenkichi, Yamaguchi Tetsuo, Uchida Sae, Izuo Naotaka, Mizoguchi Hiroyuki, Inagaki Hiroki, Kusaka Nahoko

    The Proceedings of the Annual Convention of the Japanese Psychological Association   Vol. 82 ( 0 ) page: SS-029 - SS-029   2018.9

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    DOI: 10.4992/pacjpa.82.0_ss-029

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  14. ギャンブル障害の現状と薬剤師の役割 Reviewed

    溝口 博之

    医薬ジャーナル   Vol. 54(4)   page: 1037 - 1040   2018

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  15. 創薬標的としてのnAChR:精神疾患患者で喫煙率が高い理由!?

    溝口 博之

    ファルマシア   Vol. 53 ( 9 ) page: 923 - 923   2017

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    Language:Japanese   Publisher:公益社団法人 日本薬学会  

    前頭前皮質は高次の学習記憶を司る脳部位であり,ニコチン性アセチルコリン受容体(nAChR)を介したアセチルコリン神経の投射・支配を受けている.統合失調症などの精神疾患患者は,前頭前皮質の機能が低下(hypofrontality)しており,また,喫煙率が高い傾向がある.最近,ゲノムワイド関連解析により,nAChRのα5サブユニットを司るヒト<i>CHRNA5</i>遺伝子に一塩基多型(SNP)が存在することが分かり,この変異が喫煙や統合失調症のリスクを高める可能性が報告された.基礎研究においても,マウスのα5サブユニット遺伝子を欠損させると,前頭前皮質の形態学的変化や行動に異常が生じることが報告されているが,ヒト遺伝子多型が,細胞活性あるいは神経回路にどのような影響をもたらすのか,さらには統合失調症患者で観察されるような行動障害や,hypofrontalityを引き起こすかは不明である.<br>本稿では,ヒトα5サブユニット変異体(α5SNP)を発現するマウスを用いて,α5SNPがもたらす皮質機能障害について検討したKoukouliらの研究を紹介する.<br>なお,本稿は下記の文献に基づいて,その研究成果を紹介するものである.<br>1) Tobacco and Genetics Consortium., <i>Nat</i>. <i>Genet</i>., <b>42</b>, 441–447(2010).<br>2) Schizophrenia Working Group of the Psychiatric Genomics Consortium., <i>Nature</i>, <b>511</b>, 421–427(2014).<br>3) Proulx E. <i>et</i> <i>al</i>., <i>Cell</i>. <i>Mol</i>. <i>Life</i> <i>Sci</i>., <b>71</b>, 1225-1244(2014).<br>4) Koukouli F. <i>et</i> <i>al</i>., <i>Nat</i>. <i>Med</i>., <b>23</b>, 347–354(2017).

    DOI: 10.14894/faruawpsj.53.9_923

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  16. Disrupted axon-glia interactions at the paranode in myelinated nerves cause axonal degeneration and neuronal cell death in the aged Caspr mutant mouse shambling

    Takagishi Yoshiko, Katanosaka Kimiaki, Mizoguchi Hiroyuki, Murata Yoshiharu

    NEUROBIOLOGY OF AGING   Vol. 43   page: 34 - 46   2016.7

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    Language:Japanese   Publisher:Neurobiology of Aging  

    Emerging evidence suggests that axonal degeneration is a disease mechanism in various neurodegenerative diseases and that the paranodes at the nodes of Ranvier may be the initial site of pathogenesis. We investigated the pathophysiology of the disease process in the central and peripheral nervous systems of a Caspr mutant mouse, shambling (shm), which is affected by disrupted paranodal structures and impaired nerve conduction of myelinated nerves. The shm mice manifest a progressive neurological phenotype as mice age. We found extensive axonal degeneration and a loss of neurons in the central nervous system and peripheral nervous system in aged shm mice. Axonal alteration of myelinated nerves was defined by abnormal distribution and expression of neurofilaments and derangements in the status of phosphorylated and non/de-phosphorylated neurofilaments. Autophagy-related structures were also accumulated in degenerated axons and neurons. In conclusion, our results suggest that disrupted axon-glia interactions at the paranode cause the cytoskeletal alteration in myelinated axons leading to neuronal cell death, and the process involves detrimental autophagy and aging as factors that promote the pathogenesis.

    DOI: 10.1016/j.neurobiolaging.2016.03.020

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  17. Chronic Hyponatremia Causes Neurologic and Psychologic Impairments Reviewed

    Fujisawa H, Sugimura Y, Takagi H, Mizoguchi H, Takeuchi H, Izumida H, Nakashima K, Ochiai H, Takeuchi S, Kiyota A, Fukumoto K, Iwama S, Takagishi Y, Hayashi Y, Arima H, Komatsu Y, Murata Y, Oiso Y

    Journal of the American Society of Nephrology   Vol. 27 ( 3 ) page: 766 - 80   2016.3

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    DOI: 10.1681/ASN.2014121196

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  18. Insular neural system controls decision-making in healthy and methamphetamine-treated rats Reviewed

    Hiroyuki Mizoguchi, Kentaro Katahira, Ayumu Inutsuka, Kazuya Fukumoto, Akihiro Nakamura, Tian Wang, Taku Nagai, Jun Sato, Makoto Sawada, Hideki Ohira, Akihiro Yamanaka, Kiyofumi Yamada

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   Vol. 112 ( 29 ) page: E3930 - 9   2015.7

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    Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high-reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision-making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making.

    DOI: 10.1073/pnas.1418014112

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  19. Mice carrying a schizophrenia-associated mutation of the Arhgap10 gene are vulnerable to the effects of methamphetamine treatment on cognitive function: association with morphological abnormalities in striatal neurons. Reviewed International journal

    Kazuhiro Hada, Bolati Wulaer, Taku Nagai, Norimichi Itoh, Masahito Sawahata, Akira Sobue, Hiroyuki Mizoguchi, Daisuke Mori, Itaru Kushima, Toshitaka Nabeshima, Norio Ozaki, Kiyofumi Yamada

    Molecular brain   Vol. 14 ( 1 ) page: 21 - 21   2021.1

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    We recently found a significant association between exonic copy-number variations in the Rho GTPase activating protein 10 (Arhgap10) gene and schizophrenia in Japanese patients. Special attention was paid to one patient carrying a missense variant (p.S490P) in exon 17, which overlapped with an exonic deletion in the other allele. Accordingly, we generated a mouse model (Arhgap10 S490P/NHEJ mice) carrying a missense variant and a coexisting frameshift mutation. We examined the spatiotemporal expression of Arhgap10 mRNA in the brain and found the highest expression levels in the cerebellum, striatum, and nucleus accumbens (NAc), followed by the frontal cortex in adolescent mice. The expression levels of phosphorylated myosin phosphatase-targeting subunit 1 and phosphorylated p21-activated kinases in the striatum and NAc were significantly increased in Arhgap10 S490P/NHEJ mice compared with wild-type littermates. Arhgap10 S490P/NHEJ mice exhibited a significant increase in neuronal complexity and spine density in the striatum and NAc. There was no difference in touchscreen-based visual discrimination learning between Arhgap10 S490P/NHEJ and wild-type mice, but a significant impairment of visual discrimination was evident in Arhgap10 S490P/NHEJ mice but not wild-type mice when they were treated with methamphetamine. The number of c-Fos-positive cells was significantly increased after methamphetamine treatment in the dorsomedial striatum and NAc core of Arhgap10 S490P/NHEJ mice. Taken together, these results suggested that schizophrenia-associated Arhgap10 gene mutations result in morphological abnormality of neurons in the striatum and NAc, which may be associated with vulnerability of cognition to methamphetamine treatment.

    DOI: 10.1186/s13041-021-00735-4

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  20. Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer's disease. Reviewed International journal

    Akira Sobue, Okiru Komine, Yuichiro Hara, Fumito Endo, Hiroyuki Mizoguchi, Seiji Watanabe, Shigeo Murayama, Takashi Saito, Takaomi C Saido, Naruhiko Sahara, Makoto Higuchi, Tomoo Ogi, Koji Yamanaka

    Acta neuropathologica communications   Vol. 9 ( 1 ) page: 1 - 1   2021.1

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    Microglia-mediated neuroinflammation has been implicated in the pathogenesis of Alzheimer's disease (AD). Although microglia in aging and neurodegenerative disease model mice show a loss of homeostatic phenotype and activation of disease-associated microglia (DAM), a correlation between those phenotypes and the degree of neuronal cell loss has not been clarified. In this study, we performed RNA sequencing of microglia isolated from three representative neurodegenerative mouse models, AppNL-G-F/NL-G-F with amyloid pathology, rTg4510 with tauopathy, and SOD1G93A with motor neuron disease by magnetic activated cell sorting. In parallel, gene expression patterns of the human precuneus with early Alzheimer's change (n = 11) and control brain (n = 14) were also analyzed by RNA sequencing. We found that a substantial reduction of homeostatic microglial genes in rTg4510 and SOD1G93A microglia, whereas DAM genes were uniformly upregulated in all mouse models. The reduction of homeostatic microglial genes was correlated with the degree of neuronal cell loss. In human precuneus with early AD pathology, reduced expression of genes related to microglia- and oligodendrocyte-specific markers was observed, although the expression of DAM genes was not upregulated. Our results implicate a loss of homeostatic microglial function in the progression of AD and other neurodegenerative diseases. Moreover, analyses of human precuneus also suggest loss of microglia and oligodendrocyte functions induced by early amyloid pathology in human.

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  21. Analysis of Reelin signaling and neurodevelopmental trajectory in primary cultured cortical neurons with RELN deletion identified in schizophrenia. Invited Reviewed

    Tsuneura Y, Sawahata M, Itoh N, Miyajima R, Mori D, Kohno T, Hattori M, Sobue A, Nagai T, Mizoguchi H, Nabeshima T, Ozaki N, Yamada K

    Neurochemistry International.   Vol. 144   page: 104954   2021.1

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  22. Touchscreen-based location discrimination and paired associate learning tasks detect cognitive impairment at an early stage in an App knock-in mouse model of Alzheimer's disease Reviewed

    Saifullah Md. Ali Bin, Komine Okiru, Dong Yutao, Fukumoto Kazuya, Sobue Akira, Endo Fumito, Saito Takashi, Saido Takaomi C., Yamanaka Koji, Mizoguchi Hiroyuki

    MOLECULAR BRAIN   Vol. 13 ( 1 ) page: 147   2020.11

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    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline with accumulation of amyloid beta (Aβ) and neurofibrillary tangles that usually begins 15–30 years before clinical diagnosis. Rodent models that recapitulate aggressive Aβ and/or the pathology of neurofibrillary tangles are essential for AD research. Accordingly, non-invasive early detection systems in these animal models are required to evaluate the phenotypic changes, elucidate the mechanism of disease progression, and facilitate development of novel therapeutic approaches. Although many behavioral tests efficiently reveal cognitive impairments at the later stage of the disease in AD models, it has been challenging to detect such impairments at the early stage. To address this issue, we subjected 4–6-month-old male AppNL−G−F/NL−G−F knock-in (App-KI) mice to touchscreen-based location discrimination (LD), different object–location paired-associate learning (dPAL), and reversal learning tests, and compared the results with those of the classical Morris water maze test. These tests are mainly dependent on the brain regions prone to Aβ accumulation at the earliest stages of the disease. At 4–6 months, considered to represent the early stage of disease when mice exhibit initial deposition of Aβ and slight gliosis, the classical Morris water maze test revealed no difference between groups, whereas touchscreen-based LD and dPAL tasks revealed significant impairments in task performance. Our report is the first to confirm that a systematic touchscreen-based behavioral test battery can sensitively detect the early stage of cognitive decline in an AD-linked App-KI mouse model. This system could be applied in future translational research.

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  23. Methamphetamine use causes cognitive impairment and altered decision-making Reviewed

    Mizoguchi Hiroyuki, Yamada Kiyofumi

    NEUROCHEMISTRY INTERNATIONAL   Vol. 124   page: 106 - 113   2019.3

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    Methamphetamine is a widely abused psychostimulant. It reverses transport through the dopamine transporter, thereby increasing the extracellular level of dopamine in the brain, which is associated with the rewarding effect. Repeated intake of methamphetamine leads to drug addiction, a chronically relapsing disorder characterized by compulsive drug taking, inability to limit intake, and intense drug cravings. The molecular and cellular mechanisms of drug addiction are not well understood, but have been proposed to involve neural plasticity and the remodeling of specific brain circuits. Accumulating evidence also indicates that patients addicted to methamphetamine exhibit impaired cognitive functions such as executive function, attention, social cognition, flexibility, and working memory. Furthermore, decision-making is altered in patients with drug addiction, including methamphetamine abusers. Cognitive impairment as well as altered decision-making in methamphetamine abusers may contribute to the high rate of relapse even after long-term withdrawal with psychosocial support. In this article, we review the effect of methamphetamine on cognition and decision-making in rodents. We also discuss possible mechanisms underlying cognition and decision-making impairments, including neuronal circuits, molecular and cellular events, and action control, as well as potential therapeutic targets.

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  24. AN OPERANT TASK FOR TESTING RISKY DECISION-MAKING IN MICE

    Wang T., Fukumoto K., Mizoguchi H., Yamada K.

    ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH   Vol. 42   page: 48A-48A   2018.8

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  25. AN OPERANT TASK FOR TESTING RISKY DECISION-MAKING IN MICE

    Wang T, Fukumoto K, Mizoguchi H, Yamada K

    ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH   Vol. 42   page: 48A-48A   2018.8

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  26. GAP junction/hemichannel blockers ameliorate the disease progression of FTLD/ALS mice

    Takeuchi H, Mizoguchi H, Tanaka F, Suzumura A

    JOURNAL OF THE NEUROLOGICAL SCIENCES   Vol. 381   page: 714-715 - 715   2017.10

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    DOI: 10.1016/j.jns.2017.08.2013

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  27. Hypothalamic peptidergic neurons regulates sleep/wakefulness and memory

    Izawa S., Inoue R., Mukai Y., Terao A., Chowdhury S., Mizoguchi H., Yamanaka A.

    JOURNAL OF SLEEP RESEARCH   Vol. 25   page: 115 - 116   2016.9

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  28. Disrupted axon-glia interactions at the paranode in myelinated nerves cause axonal degeneration and neuronal cell death in the aged Caspr mutant mouse shambling. Reviewed

    Takagishi Y, Katanosaka K, Mizoguchi H, Murata Y

    Neurobiology of Aging   Vol. 43   page: 34-46   2016.7

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    DOI: 10.1016/j.neurobiolaging.2016.03.020.

  29. Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

    Fujisawa Haruki, Sugimura Yoshihisa, Takagi Hiroshi, Mizoguchi Hiroyuki, Takeuchi Hideyuki, Izumida Hisakazu, Nakashima Kohtaro, Ochiai Hiroshi, Takeuchi Seiji, Kiyota Atsushi, Fukumoto Kazuya, Iwama Shintaro, Takagishi Yoshiko, Hayashi Yoshitaka, Arima Hiroshi, Komatsu Yukio, Murata Yoshiharu, Oiso Yutaka

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   Vol. 27 ( 3 ) page: 766 - 780   2016.3

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  30. Usefulness of DREADD technology combined with adeno-associated virus vector in behavioral pharmacology

    Mizoguchi Hiroyuki, Yamanaka Akihiro, Yamada Kiyofumi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 130 ( 3 ) page: S73 - S73   2016.3

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  31. The insular neural system controls decision-making in healthy and drug-dependent rats

    Mizoguchi Hiroyuki, Yamada Kiyofumi

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 128 ( 3 ) page: S61 - S61   2015.7

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  32. Thyrotoropin receptor knockout changes monoaminergic neuronal system and produces methylphenidate-sensitive emotional and cognitive dysfunction. Reviewed

    Mouri A, Hoshino Y, Narusawa S, Ikegami K, Mizoguchi H, Murata Y, Yoshimura T, Nabeshima T

    Psychoneuroendocrinology   Vol. 48   page: 147-161   2014.10

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    Attention deficit/hyperactivity disorder (ADHD) has been reported in association with resistance to thyroid hormone, a disease caused by a mutation in the thyroid hormone receptor β (TRβ) gene. TRβ is a key protein mediating down-regulation of thyrotropin (TSH) expression by 3,3',5-tri-iodothyronine (T3), an active form of thyroid hormone. Dysregulation of TSH and its receptor (TSHR) is implicated in the pathophysiology of ADHD but the role of TSHR remains elusive. Here, we clarified a novel role for TSHR in emotional and cognitive functions related to monoaminergic nervous systems. TSHR knockout mice showed phenotypes of ADHD such as hyperactivity, impulsiveness, a decrease in sociality and increase in aggression, and an impairment of short-term memory and object recognition memory. Administration of methylphenidate (1, 5 and 10mg/kg) reversed impulsiveness, aggression and object recognition memory impairment. In the knockout mice, monoaminergic changes including decrease in the ratio of 3-methoxy-4-hydroxyphenylglycol/noradrenaline and increase in the ratio of homovanillic acid/dopamine were observed in some brain regions, accompanied by increase in the expression of noradrenaline transporter in the frontal cortex. When TSH was completely suppressed by the supraphysiological administration of T3 to the adult mice, some behavioral and neurological changes in TSHR KO mice were also observed, suggesting that these changes were not due to developmental hypothyroidism induced by the inactivation of TSHR but to the loss of the TSH-TSHR pathway itself. Taken together, the present findings suggest a novel role for TSHR in behavioral and neurological phenotypes of ADHD.

    DOI: 10.1016/j.psyneuen.2014.05.021

  33. Granulocyte-Colony Stimulating Factor Attenuates Oligomeric Amyloid β Neurotoxicity by Activation of Neprilysin Reviewed

    Doi Y, Takeuchi H, Mizoguchi H, Fukumoto K, Horiuchi H, Jin S, Kawanokuchi J, Parajuli B, Sonobe Y, Mizuno T, Suzumura A

    PLoS One   Vol. 9 ( 7 ) page: e103458   2014.7

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    Soluble oligomeric amyloid β (oAβ) causes synaptic dysfunction and neuronal cell death, which are involved in the pathogenesis of Alzheimer's disease (AD). The hematopoietic growth factor granulocyte-colony stimulating factor (G-CSF) is expressed in the central nervous system (CNS) and drives neurogenesis. Here we show that G-CSF attenuated oAβ neurotoxicity through the enhancement of the enzymatic activity of Aβ-degrading enzyme neprilysin (NEP) in neurons, while the NEP inhibitor thiorphan abolished the neuroprotection. Inhibition of MEK5/ERK5, a major downstream effector of G-CSF signaling, also ablated neuroprotective effect of G-CSF. Furthermore, intracerebroventricular administration of G-CSF enhanced NEP enzymatic activity and clearance of Aβ in APP/PS1 transgenic mice. Thus, we propose that G-CSF may be a possible therapeutic strategy against AD.

    DOI: 10.1371/journal.pone.0103458

  34. Fingolimod increases brain-derived neurotrophic factor levels and ameliorates amyloid β-induced memory impairment. Reviewed

    Fukumoto K, Mizoguchi H, Takeuchi H, Horiuchi H, Kawanokuchi J, Jin S, Mizuno T, Suzumura A.

    Behav. Brain Res.   Vol. 268   page: 88-93   2014.7

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    Alzheimer's disease is a progressive neurodegenerative disorder. Amyloid β, a neurotoxic protein, causes disruption of hippocampal synaptic plasticity, and induces cognitive impairment in Alzheimer's disease. We previously revealed that fingolimod, a new oral immunosuppressant used to treat multiple sclerosis, ameliorates oligomeric amyloid β-induced neuronal damage via up-regulation of neuronal brain-derived neurotrophic factor (BDNF). Here, we showed that oral administration of fingolimod ameliorated the impairment in object recognition memory and associative learning in mice injected with amyloid β. This effect was associated with restoration of normal BDNF expression levels in the cerebral cortices and hippocampi, suggesting that neuroprotection was mediated by up-regulation of neuronal BDNF levels. Therefore, fingolimod may provide therapeutic effects in patients with Alzheimer's disease.

  35. Astroglial IFITM3 mediates neuronal impairments following neonatal immune challenge in mice Reviewed

    Ibi D, Nagai T, Nakajima A, Mizoguchi H, Kawase T, Tsuboi D, Kano S, Sato Y, Hayakawa M, Lange UC, Adams DJ, Surani MA, Satoh T, Sawa A, Kaibuchi K, Nabeshima T, Yamada K.

    Glia   Vol. 61 ( 5 ) page: 679-693   2013

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    Interferon-induced transmembrane protein 3 (IFITM3) ıplays a crucial role in the antiviral responses of Type I interferons (IFNs). The role of IFITM3 in the central nervous system (CNS) is, however, largely unknown, despite the fact that its expression is increased in the brains of patients with neurologic and neuropsychiatric diseases. Here, we show the role of IFITM3 in long-lasting neuronal impairments in mice following polyriboinosinic-polyribocytidylic acid (polyI:C, a synthetic double-stranded RNA)-induced immune challenge during the early stages of development. We found that the induction of IFITM3 expression in the brain of mice treated with polyI:C was observed only in astrocytes. Cultured astrocytes were activated by polyI:C treatment, leading to an increase in the mRNA levels of inflammatory cytokines as well as Ifitm3. When cultured neurons were treated with the conditioned medium of polyI:C-treated astrocytes (polyI:C-ACM), neurite development was impaired. These polyI:C-ACM-induced neurodevelopmental abnormalities were alleviated by ifitm3(-/-) astrocyte-conditioned medium. Furthermore, decreases of MAP2 expression, spine density, and dendrite complexity in the frontal cortex as well as memory impairment were evident in polyI:C-treated wild-type mice, but such neuronal impairments were not observed in ifitm3(-) (/) (-) mice. We also found that IFITM3 proteins were localized to the early endosomes of astrocytes following polyI:C treatment and reduced endocytic activity. These findings suggest that the induction of IFITM3 expression in astrocytes by the activation of the innate immune system during the early stages of development has non-cell autonomous effects that affect subsequent neurodevelopment, leading to neuropathological impairments and brain dysfunction, by impairing endocytosis in astrocytes.

    DOI: 10.1002/glia.22461

  36. Roles of Matrix Metalloproteinases and Their Targets in Epileptogenesis and Seizures. Reviewed

    Mizoguchi H, Yamada K.

    Clinical Psychopharmacology and Neuroscience   Vol. 11 ( 2 ) page: 45-52   2013

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    Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) remodel the pericellular environment by regulating the cleavage of extracellular matrix proteins, cell surface components, neurotransmitter receptors, and growth factors, which together regulate cell adhesion, synaptogenesis, synaptic plasticity, and long-term potentiation. Increased MMP activity and dysregulation of the balance between MMPs and TIMPs have also been implicated in various pathological conditions. Recent studies have suggested that prolonged seizures are associated with high MMP levels in serum and neural tissues, and certain extracellular macromolecule targets may influence the pathogenesis of epilepsy and seizure. In this review, we discuss the roles of MMP activation in animal models of epilepsy.

  37. Placental extract improves hippocampal neuronal loss and fear memory impairment resulting from chronic restraint stress in ovariectomized mice. Reviewed

    Takuma K, Mizoguchi H, Funatsu Y, Kitahara Y, Ibi D, Kamei H, Matsuda T, Koike K, Inoue M, Nagai T and Yamada K.

    J Pharmacol Sci.   Vol. 120 ( 2 ) page: 89-97   2012

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  38. Involvement of matrix metalloproteinase-9 in the development of morphine tolerance. Reviewed

    Nakamoto K, Kawasaki S, Kobori T, Fujita-Hamabe W, Mizoguchi H, Yamada K, Nabeshima T and Tokuyama S.

    Eur J Pharmacol.   Vol. 683   page: 86-92   2012

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  39. Combination of chronic stress and ovariectomy causes conditioned fear memory deficits and hippocampal cholinergic neuronal loss in mice.

    Takuma K, Mizoguchi H, Funatsu Y, Hoshina Y, Himeno Y, Fukuzaki E, Kitahara Y, Arai S, Ibi D, Kamei H, Matsuda T, Koike K, Inoue M, Nagai T and Yamada K.

    Neuroscience.   Vol. 207   page: 261-273   2012

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  40. Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-β peptide in mice. Reviewed

    Furukawa-Hibi Y, Alkam T, Nitta A, Matsuyama A, Mizoguchi H, Suzuki K, Moussaoui S, Yu QS, Greig NH, Nagai T, Yamada K.

    Behav. Brain Res.   Vol. 225 ( 1 ) page: 222-229   2011.11

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    The cholinesterase inhibitor, rivastigmine, ameliorates cognitive dysfunction and is approved for the treatment of Alzheimer's disease (AD). Rivastigmine is a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE); however, the impact of BuChE inhibition on cognitive dysfunction remains to be determined. We compared the effects of a selective BuChE inhibitor, N1-phenethyl-norcymserine (PEC), rivastigmine and donepezil (an AChE-selective inhibitor) on cognitive dysfunction induced by amyloid-β peptide (Aβ(1-40)) in mice. Five-week-old imprinting control region (ICR) mice were injected intracerebroventricularly (i.c.v.) with either Aβ(1-40) or the control peptide Aβ(40-1) on Day 0, and their recognition memory was analyzed by a novel object recognition test. Treatment with donepezil (1.0mg/kg), rivastigmine (0.03, 0.1, 0.3mg/kg) or PEC (1.0, 3.0mg/kg) 20min prior to, or immediately after the acquisition session (Day 4) ameliorated the Aβ(1-40) induced memory impairment, indicating a beneficial effect on memory acquisition and consolidation. In contrast, none of the investigated drugs proved effective when administrated before the retention session (Day 5). Repeated daily administration of donepezil, rivastigmine or PEC, on Days 0-3 inclusively, ameliorated the cognitive dysfunction in Aβ(1-40) challenged mice. Consistent with the reversal of memory impairments, donepezil, rivastigmine or PEC treatment significantly reduced Aβ(1-40) induced tyrosine nitration of hippocampal proteins, a marker of oxidative damage. These results indicate that BuChE inhibition, as well as AChE inhibition, is a viable therapeutic strategy for cognitive dysfunction in AD.

  41. Low barometric pressure aggravates neuropathic pain in guinea pigs. Reviewed

    Sato J, Itano Y, Funakubo M, Mizoguchi H, Itoh M, Mori R.

    Neurosci. Lett.   Vol. 503 ( 2 ) page: 152-156   2011.10

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    Several clinical studies have demonstrated a consistent relationship between changes in meteorological factors, particularly barometric pressure, and pain intensity in subjects with chronic pain. We have previously demonstrated that exposure to artificially low barometric pressure (LP) intensifies pain-related behaviors in rats with neuropathic pain. In the present study, guinea pigs with unilateral L5 spinal nerve ligation (SNL) were placed in a pressure-controlled chamber and subjected to LP of 10 or 27hPa below the ambient pressure. The SNL surgery led to increased hindpaw withdrawal frequencies to 34-, 59-, and 239-mN von Frey filaments (VFFs). When the SNL animals were subjected to both LP exposures consecutively, the hindpaw withdrawal frequencies further increased; the effect was most significant when the animals were exposed to LP 27hPa below ambient pressure. In contrast, no change was seen in a group of sham-operated control animals. These results indicate that fluctuations in LP within the range of natural weather patterns can potentiate neuropathic pain in guinea pigs.

  42. Interleukin-34 selectively enhances the neuroprotective effects of microglia to attenuate oligomeric amyloid-β neurotoxicity. Reviewed

    Mizuno T, Doi Y, Mizoguchi H, Jin S, Noda M, Sonobe Y, Takeuchi H, Suzumura A.

    Am J Pathol.   Vol. 179 ( 4 ) page: 2016-2027   2011.10

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  43. Matrix metalloproteinase-9 contributes to kindled seizure development in pentylenetetrazole-treated mice by converting pro-BDNF to mature BDNF in the hippocampus. Reviewed

    Mizoguchi H, Nakade J, Tachibana M, Ibi D, Someya E, Koike H, Kamei H, Nabeshima T, Itohara S, Takuma K, Sawada M, Sato J, Yamada K.

    J Neurosci.   Vol. 31 ( 36 ) page: 12963-12971   2011.9

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  44. Nicotine ameliorates impairment of working memory in methamphetamine-treated rats. Reviewed

    Mizoguchi H, Ibi D, Takase F, Nagai T, Kamei H, Toth E, Sato J, Takuma K, Yamada K.

    Behav Brain Res.   Vol. 220 ( 1 ) page: 159-163   2011.6

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  45. Lowering barometric pressure aggravates depression-like behavior in rats. Reviewed

    Mizoguchi H, Fukaya K, Mori R, Itoh M, Funakubo M, Sato J.

    Behav Brain Res.   Vol. 218   page: 190-193   2011.3

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  46. Pharmacologic treatment with GABAB receptor agonist of methamphetamine-induced cognitive impairment in mice.BBB Reviewed

    Mizoguchi H, Yamada K.

    Current Neuropharmacol.   Vol. 9 ( 1 ) page: 109-112   2011.3

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  47. Involvement of matrix metalloproteinase-mediated proteolysis of neural cell adhesion molecule in the development of cerebral ischemic neuronal damage. Reviewed

    Shichi K, Fujita-Hamabe W, Harada S, Mizoguchi H, Yamada K, Nabeshima T, Tokuyama S.

    J Pharmacol Exp Ther.     page: in press   2011

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  48. Matrix metalloproteinases contribute to neuronal dysfunction in animal models of drug dependence, Alzheimer's disease, and epilepsy.

    Mizoguchi H, Yamada K, Nabeshima T.

    Biochem Res Internat.     page: 681385   2011

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  49. Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer's disease. Reviewed

    Takeuchi H, Mizoguchi H, Doi Y, Jin S, Noda M, Liang J, Li H, Zhou Y, Mori R, Yasuoka S, Li E, Parajuli B, Kawanokuchi J, Sonobe Y, Sato J, Yamanaka K, Sobue G, Mizuno T, Suzumura A.

    PLoS One.   Vol. 6 ( 6 ) page: e21108   2011

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  50. Chronic restraint stress impairs neurogenesis and hippocampus-dependent fear memory in mice: possible involvement of a brain-specific transcription factor Npas4. Reviewed

    Yun J, Koike H, Ibi D, Toth E, Mizoguchi H, Nitta A, Yoneyama M, Ogita K, Yoneda Y, Nabeshima T, Nagai T, Yamada K.

    J Neurochem.   Vol. 114 ( 6 ) page: 1840-1851   2010.9

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  51. Oral supplementation with Leu-Ile, a hydrophobic dipeptide, prevents the impairment of memory induced by amyloid beta in mice via restraining the hyperphosphorylation of extracellular signal-regulated kinase. Reviewed

    Alkam T, Nitta A, Furukawa-Hibi Y, Niwa M, Mizoguchi H, Yamada K, Nabeshima T.

    Behav Brain Res.   Vol. 210 ( 2 ) page: 184-190   2010.7

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  52. Disrupted transforming growth factor-beta signaling in spinal and bulbar muscular atrophy. Reviewed

    Katsuno M, Adachi H, Minamiyama M, Waza M, Doi H, Kondo N, Mizoguchi H, Nitta A, Yamada K, Banno H, Suzuki K, Tanaka F, Sobue G.

    J Neurosci.   Vol. 30 ( 16 ) page: 5702-5712   2010.4

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  53. Alterations of emotional and cognitive behaviors in matrix metalloproteinase-2 and -9-deficient mice. Reviewed

    Mizoguchi H., Ibi D., Takuma K., Toth E., Sato J., Itohara S, Nabeshima T, Yamada K.

    The Open Behav Sci J.   Vol. 4   page: 19-25   2010.4

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  54. Combined effect of neonatal immune activation and mutant DISC1 on phenotypic changes in adulthood. Reviewed

    Ibi D, Nagai T, Koike H, Kitahara Y, Mizoguchi H, Niwa M, Jaaro-Peled H, Nitta A, Yoneda Y, Nabeshima T, Sawa A, Yamada K.

      Vol. 206 ( 1 ) page: 32-37   2010.1

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  55. Therapeutic potential of nicotine for methamphetamine-induced impairment of sensorimotor gating: Involvement of pallidotegmental neurons. Reviewed

    Mizoguchi H, Arai S, Koike H, Ibi D, Kamei H, Nabeshima T, Kim HC, Takuma K, and Yamada K.

    Psychopharmacology(Berl)   Vol. 207 ( 2 ) page: 235-243   2009.12

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  56. Mice Deficient for Glucagon Gene-Derived Peptides Display Normoglycemia and Hyperplasia of Islet {alpha}-Cells But Not of Intestinal L-Cells. Reviewed

    Hayashi Y, Yamamoto M, Mizoguchi H, Watanabe C, Ito R, Yamamoto S, Sun XY, and Murata Y.

    Mol Endocrinol.   Vol. 23 ( 12 ) page: 1990-1999   2009.12

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  57. Microglia activated with toll-like receptor 9 ligand CpG attenuate oligomeric amyloid β neurotoxicity in vitro and in vivo models of Alzheimer's disease. Reviewed

    Doi Y, Mizuno T, Maki Y, Jin S, Mizoguchi H, Ikeyama M, Doi M, Michikawa M, Takeuchi H, and Suzumura A.

    Am J Pathol.   Vol. 175 ( 5 ) page: 2121-2132   2009.11

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  58. RAGE-mediated signaling contributes to intraneuronal transport of amyloid-beta and neuronal dysfunction. Reviewed

    Takuma K, Fang F, Zhang W, Yan S, Fukuzaki E, Du H, Sosunov A, McKhann G, Funatsu Y, Nakamichi N, Nagai T, Mizoguchi H, Ibi D, Hori O, Ogawa S, Stern DM, Yamada K, Yan SS.

    Proc Natl Acad Sci U S A.   Vol. 106 ( 47 ) page: 20021-20026   2009.11

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  59. *Matrix metalloprotease-9 inhibition improves amyloid β-mediated cognitive impairment and neurotoxicity in mice. Reviewed

    Mizoguchi H, Takuma K, Fukuzaki E, Ibi D, Someya E, Akazawa K, Alkam T, Tsunekawa H, Mouri A, Noda Y, Nabeshima T, and Yamada K.

    J Pharmacol Exp Ther.   Vol. 331 ( 1 ) page: 14-22   2009.10

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  60. Neonatal phencyclidine treatment in mice induces behavioral, histological and neurochemical abnormalities in adulthood. Reviewed

    Nakatani-Pawlak A, Yamaguchi K, Tatsumi Y, Mizoguchi H and Yoneda Y.

    Biol Pharm Bull.   Vol. 32 ( 9 ) page: 1576-1583   2009.9

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  61. Behavioral abnormality and pharmacologic response in social isolation-reared mice. Reviewed

    Behav Brain Res.   Vol. 202 ( 1 ) page: 114-121   2009.8

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  62. Neonatal polyI:C treatment in mice results in schizophrenia-like behavioral and neurochemical abnormalities in adulthood. Reviewed

    Ibi D, Nagai T, Kitahara Y, Mizoguchi H, Koike H, Shiraki A, Takuma K, Kamei H, Noda Y, Nitta A, Nabeshima T, Yoneda Y, and Yamada K.

    Neurosci Res.   Vol. 64 ( 3 ) page: 297-305   2009.7

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  63. GABAB receptor agonist baclofen improves methamphetamine-induced cognitive deficit in mice. Reviewed

    Arai S, Takuma K, Mizoguchi H, Ibi D, Nagai T, Kamei H, Kim HC, and Yamada K.

    Eur J Pharmacol.   Vol. 602 ( 1 ) page: 101-104   2009.1

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  64. Involvement of Pallidotegmental Neurons in Methamphetamine- and MK-801-Induced Impairment of Prepulse Inhibition of the Acoustic Startle Reflex in Mice: Reversal by GABA(B) Receptor Agonist Baclofen. Reviewed

    Arai S, Takuma K, Mizoguchi H, Ibi D, Nagai T, Takahashi K, Kamei H, Nabeshima T, and Yamada K.

    Neuropsychopharmacology   Vol. 33 ( 13 ) page: 3164-3175   2008.12

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  65. The extensive nitration of neurofilament light chain in the hippocampus is associated with the cognitive impairment induced by amyloid beta in mice. Reviewed

    Alkam T, Nitta A, Mizoguchi H, Itoh A, Murai R, Nagai T, Yamada K, and Nabeshima T.

    The Journal of Pharmacology and Experimental Therapeutics   Vol. 327 ( 1 ) page: 137-147   2008.10

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  66. Ovariectomy increases neuronal amyloid-beta binding alcohol dehydrogenase level in the mouse hippocampus. Reviewed

    Fukuzaki E, Takuma K, Funatsu Y, Himeno Y, Kitahara Y, Gu B, Mizoguchi H, Ibi D, Koike K, Inoue M, Yan SD, and Yamada K.

    Neurochem Int.   Vol. 52 ( 7 ) page: 1358-1364   2008.6

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  67. Social isolation rearing-induced impairment of the hippocampal neurogenesis is associated with deficits in spatial memory and emotion-related behaviors in juvenile mice. Reviewed

    Ibi D, Takuma K, Koike H, Mizoguchi H, Tsuritani K, Kuwahara Y, Kamei H, Nagai T, Yoneda Y, Nabeshima T, and Yamada K.

    Journal of Nuerochemistry   Vol. 105 ( 3 ) page: 921-932   2008.5

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  68. Restraining tumor necrosis factor-alpha by thalidomide prevents the amyloid beta-induced impairment of recognition memory in mice. Reviewed

    Alkam T, Nitta A, Mizoguchi H, Saito K, Seshima M, Itoh A, Yamada K, and Nabeshima T.

    Behavioural Brain Research   Vol. 189 ( 1 ) page: 100-106   2008.5

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  69. Role of tissue plasminogen activator in the sensitization of methamphetamine-induced dopamine release in the nucleus accumbens. Reviewed

    Fukakusa A, Nagai T, Mizoguchi H, Otsuka N, Kimura H, Kamei H, Kim HC, Nabeshima T, Takuma K, and Yamada K.

    Journal of Nuerochemistry   Vol. 105 ( 2 ) page: 436-444   2008.4

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  70. Enhanced activity of hippocampal BACE1 in a mouse model of postmenopausal memory deficits. Reviewed

    Fukuzaki E, Takuma K, Himeno Y, Yoshida S, Funatsu Y, Kitahara Y, Mizoguchi H, Ibi D, Koike K, Inoue M, and Yamada K.

    Neuroscience Letter   Vol. 433 ( 2 ) page: 141-145   2008.3

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  71. Improvement by minocycline of methamphetamine-induced impairment of recognition memory in mice. Reviewed

    Mizoguchi H, Takuma T, Fukakusa A, Ito Y, Nakatani A, Ibi D, Kim H-C and Yamada K.

    Psychopharmacology (Berl)   Vol. 196 ( 2 ) page: 233-241   2008.2

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  72. Tissue plasminogen activator is not involved in methamphetamine-induced neurotoxicity. Reviewed

    Fukakusa A, Mizoguchi H, Koike H, Nabeshima T, Takuma K, Yamada K.

    Journal of Pharmacological Sciences   Vol. 106 ( 2 ) page: 321-324   2008.2

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  73. Ginkgo biloba extract EGb 761 attenuates hippocampal neuronal loss and cognitive dysfunction resulting from chronic restraint stress in ovariectomized rats. Reviewed

    Takuma K, Hoshina Y, Arai S, Himeno Y, Matsuo A, Funatsu Y, Kitahara Y, Ibi D, Hayase M, Kamei H, Mizoguchi H, Nagai T, Koike K, Inoue M, and Yamada K.

    Neuroscience   Vol. 149 ( 1 ) page: 256-262   2008.1

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  74. *Neuropsychotoxicity of abused drugs: involvement of matrix metalloproteinase-2 and -9 and tissue inhibitor of matrix metalloproteinase-2 in methamphetamine-induced behavioral sensitization and reward in rodents. Reviewed

    Mizoguchi H, Yamada K, and Nabeshima T.

    Journal of Pharmacological Sciences   Vol. 106 ( 1 ) page: 9-14   2008.1

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  75. Activation of post-synaptic dopamine D(1) receptors promotes the release of tissue plasminogen activator in the nucleus accumbens via PKA signaling. Reviewed

    Ito M, Nagai T, Mizoguchi H, Sato K, Hayase M, Otsuka N, Fukakusa A, Kumagai N, Kim HC, Nabeshima T, Takuma K, and Yamada K.

    Journal of Neurochemistry   Vol. 17   2007.10

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  76. Repeated methamphetamine treatment impairs spatial working memory in rats: reversal by clozapine but not haloperidol. Reviewed

    Nagai T, Takuma K, Dohniwa M, Ibi D, Mizoguchi H, Kamei H, Nabeshima T, Yamada K.

    Psychopharmacology (Berl)   Vol. 194 ( 1 ) page: 21-32   2007.9

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  77. *Role of matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) in methamphetamine-induced behavioral sensitization and reward: Implications for dopamine receptor downregulation and dopamine release Reviewed

    Mizoguchi H, Yamada K, Mouri A, Niwa M, Mizuno T, Noda Y, Nitta A, Itohara S, Banno Y, and Nabeshima T.

    Journal of Neurochemistry   Vol. 102 ( 5 ) page: 1548-1560   2007.9

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  78. A novel molecule "shati" is involved in methamphetamine-induced hyperlocomotion, sensitization, and conditioned place preference. Reviewed

    Niwa M, Nitta A, Mizoguchi H, Ito Y, Noda Y, Nagai T, and Nabeshima T.

    Journal of Neuroscience   Vol. 27 ( 28 ) page: 7604-7615   2007.7

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  79. Neural circuits containing pallidotegmental GABAergic neurons are involved in the prepulse inhibition of the startle reflex in mice Reviewed

    Takahashi K, Nagai T, Kamei H, Maeda K, Matsuya T, Arai S, Mizoguchi H, Yoneda Y, Nabeshima T, Takuma K, and Yamada K.

    Biological Psychiatry   Vol. 62 ( 2 ) page: 148-157   2007.7

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  80. Oral vaccination with a viral vector containing A{beta} cDNA attenuates age-related A{beta} accumulation and memory deficits without causing inflammation in a mouse Alzheimer model Reviewed

    Mouri A, Noda Y, Hara H, Mizoguchi H, Tabira T, and Nabeshima T.

    Journal of Federation of American Societies for Experimental Biology   Vol. 21 ( 9 ) page: 2135-2148   2007.7

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  81. A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Abeta(25-35). Reviewed

    Alkam T, Nitta A, Mizoguchi H, Itoh A, and Nabeshima T.

    Behavioural Brain Research   Vol. 180 ( 2 ) page: 139-145   2007.6

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  82. The allosteric potentiation of nicotinic acetylcholine receptors by galantamine ameliorates the cognitive dysfunction in beta amyloid (25-35) i.c.v.-injected mice: involvement of dopaminergic systems Reviewed

    Wang D, Noda Y, Zhou Y, Mouri A, Mizoguchi H, Nitta A, Chen W, and Nabeshima T.

    Neuropsychopharmacology   Vol. 32 ( 6 ) page: 1261-1271   2007.6

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  83. Possible involvement of protease-activated receptor-1 in the regulation of morphine-induced dopamine release and hyperlocomotion by the tissue plasminogen activator-plasmin system Reviewed

    Ito M, Nagai T, Mizoguchi H, Fukakusa A, Nakanishi Y, Kamei H, Nabeshima T, Takuma K, and Yamada K.

    Journal of Nuerochemistry   Vol. 101 ( 5 ) page: 1392-1399   2007.6

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  84. 17beta-Estradiol attenuates hippocampal neuronal loss and cognitive dysfunction induced by chronic restraint stress in ovariectomized rats Reviewed

    Takuma K, Matsuo A, Himeno Y, Hoshina Y, Ohno Y, Funatsu Y, Arai S, Kamei H, Mizoguchi H, Nagai T, Koike K, Inoue M, and Yamada K.

    Neuroscience   Vol. 146 ( 1 ) page: 60-68   2007.4

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  85. Reinforcing effects of morphine are reduced in tissue plasminogen activator-knockout mice Reviewed

    Yan Y, Yamada K, Mizoguchi H, Noda Y, Nagai T, Nitta A, and Nabeshima T.

    Neuroscience   Vol. 146 ( 1 ) page: 50-59   2007.4

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  86. *Reduction of methamphetamine-induced sensitization and reward in matrix metalloproteinase-2 and -9-deficient mice Reviewed

    Mizoguchi H, Yamada K, Niwa M, Mouri A, Mizuno T, Noda Y, Nitta A, Itohara S, Banno Y, and Nabeshima T.

    Journal of Neurochemistry   Vol. 100 ( 6 ) page: 1579-1588   2007.3

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  87. Dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via extracellular signal-regulated kinase 1/2 in the prefrontal cortex Reviewed

    Nagai T, Takuma K, Kamei H, Ito Y, Nakamichi N, Ibi D, Nakanishi Y, Murai M, Mizoguchi H, Nabeshima T, and Yamada K.

    Learning & Memory   Vol. 14 ( 3 ) page: 117-125   2007.3

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  88. Clozapine prevents a decrease in neurogenesis in mice repeatedly treated with phencyclidine Reviewed

    Maeda K, Sugino H, Hirose T, Kitagawa H, Nagai T, Mizoguchi H, Takuma K, and Yamada K

    Journal of Pharmacological Sceiences   Vol. 103 ( 3 ) page: 299-308   2007.3

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  89. Synergistic effects of adenosine A (2A) antagonist and L-DOPA on rotational behaviors in 6-hydrocydopamine-induced hemi-parkinsonian mouse model Reviewed

    4. Matsuya T, Takuma K, Sato K, Asai M, Murakami Y, Miyoshi S, Noda A, Nagai T, Mizoguchi H, Nabeshima S, and Yamada K.

    Journal of Pharmacological Sciences   Vol. 103 ( 3 ) page: 329-332   2007.3

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  90. A novel azaindolizinone derivative ASET1446 (spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one) improves methamphetamine-induced impairment of recognition memory in mice by activating extracellular signal-regulated kinase 1/2 Reviewed

    Ito Y, Takuma K, Mizoguchi H, Nagai T, and Yamada K.

    The Journal of Pharmacology and Experimental Therapeutics   Vol. 320 ( 2 ) page: 819-827   2007.2

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  91. The rewards of nicotine: regulation by tissue plasminogen activator-plasmin system through protease activated receptor-1 Reviewed

    Nagai T, Ito M, Nakamichi N, Mizoguchi H, Kamei H, Fukakusa A, Nabeshima T, Takuma K, and Yamada K.

    Journal of Neuroscience   Vol. 26 ( 47 ) page: 12374-12383   2006.11

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  92. Effects of single and repeated administration of methamphetamine or morphine on neuroglycan C gene expression in the rat brain Reviewed

    Ishikawa K, Nitta A, Mizoguchi H, Mouri A, Murai R, Miyamoto Y, Noda Y, Kitaichi K, Yamada K, and Nabeshima T

    The International Journal of Neuropsychopharmacology   Vol. 9 ( 4 ) page: 407-415   2006.8

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  93. Inhibition of neprilysin by infusion of thiorphan into the hippocampus causes an accumulation of amyloid Beta and impairment of learning and memory Reviewed

    Zou LB, Mouri A, Iwata N, Saido TC, Wang D, Wang MW, Mizoguchi H, Noda Y, and Nabeshima T.

    The Journal of Pharmacology and Experimental Therapeutics   Vol. 317 ( 1 ) page: 334-340   2006.4

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  94. Relapse of methamphetamine-seeking behavior in C57BL/6J mice demonstrated by a reinstatement procedure involving intravenous self-administration Reviewed

    Yan Y, Nitta A, Mizoguchi H, Yamada K, and Nabeshima T.

    Behavioural Brain Research   Vol. 168 ( 1 ) page: 137-143   2006.3

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  95. Dysfunction of glutamatergic systems and potential animal models of schizophrenia Reviewed

    Mouri A, Noda Y, Mizoguchi H and Nabeshima T.

    Nippon Yakurigaku Zasshi   Vol. 127 ( 1 ) page: 4-8   2006.1

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  96. Evaluation methods for the discriminative stimulus and possible mechanisms of discriminative stimulus effects of methamphetamine in the rat Invited

    Mizoguchi H, Noda Y and Nabeshima T.

    Nippon Yakurigaku Zasshi   Vol. 126 ( 1 ) page: 17-23   2005.7

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  97. *Regulations of methamphetamine reward by extracellular signal-regulated kinase 1/2/ets-like gene-1 signaling pathway via the activation of dopamine receptors Reviewed

    Mizoguchi H, Yamada K, Mizuno M, Mizuno T, Nitta A, Noda Y, and Nabeshima T.

    Molecular Pharmacology   Vol. 65 ( 5 ) page: 1293-1301   2004.5

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  98. Protection by constitutively formed nitric oxide of intestinal damage induced by indomethacin in rats Reviewed

    Tanaka A, Mizoguchi H, Kunikata T, Miyazawa T, and Takeuchi K.

    Journal of Physiology-Paris   Vol. 95 ( 1-6 ) page: 35-41   2001.12

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  99. Protection by aspirin of indomethacin-induced small intestinal damage in rats: Mediation by salicylic acid Reviewed

    Takeuchi K, Hase S, Mizoguchi H, Komoike Y, and Tanaka A.

    Journal of Physiology-Paris   Vol. 95 ( 1-6 ) page: 51-57   2001.12

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  100. Protective effect of rebamipide on indomethacine-induced intestinal damage in rats Reviewed

    Mizoguchi H, Ogawa Y, Kanatsu K, Tanaka A, Kato S, and Takeuchi K

    Journal of Gastroenterology and Hepatology   Vol. 16 ( 10 ) page: 1112-1119   2001.10

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  101. Intestinal protection by lafutidine, a histamine H(2)-receptor antagonist, against indomethacin-induced damage in rats-role of endogenous nitric oxide Reviewed

    Tanaka A, Mizoguchi H, Hase S, Miyazawa T, and Takeuchi K

    Medical Sceience Monitor   Vol. 7 ( 5 ) page: 869-877   2001.9

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  102. Lack of Gastric Toxicity of Nitric Oxide-Releasing Indomethacin, NCX-530, in Experimental Animals Reviewed

    Takeuchi K, Mizoguchi H, Araki H, Komoike Y, and Suzuki K

    Digest Disease Science   Vol. 46 ( 8 ) page: 1805-1818   2001.8

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  103. Monochloramine impairs mucosal blood flow response and healing of gastric lesions in rats: relation to capsaicin-sensitive sensory neurons Reviewed

    Takeuchi K, Suzuki K, Mizoguchi H, Araki H, and Nishiwaki H

    Journal of Gastroenterology and Hepatology   Vol. 16 ( 3 ) page: 282-289   2001.3

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  104. Lack of small intestinal toxicity of nitric oxide-releasing indomethacin, NCX-530, in rats Reviewed

    Mizoguchi H, Hase S, Tanaka A, and Takeuchi K

    Alimentary Pharmacology & Therapeutics   Vol. 15 ( 2 ) page: 257-267   2001.2

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  105. Gastrointestinal sparing anti-inflammatory drugs-effects on ulcerogenic and healing responses Reviewed

    Takeuchi K, Tanaka A, Suzuki K, and Mizoguchi H

    Current Pharmaceutical Design   Vol. 7 ( 1 ) page: 49-69   2001.1

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  106. 一酸化窒素遊離型インドメタシンの小腸傷害性についての検討

    溝口博之, 田中晶子, 竹内孝治

    Ulcer Research   Vol. 28   page: 157-160   2001

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  107. Prostaglandin E inhibits indomethacin-induced gastric lesions through EP1 receptors. Reviewed

    Suzuki K, Araki H, Mizoguchi H, Furukawa O, and Takeuchi K

    Digestion   Vol. 63 ( 2 ) page: 92-101   2001

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  108. The roles of nitric oxide and prostaglandins in alterations of ulcerogenic and healing responses in adjuvant-induced arthritic rat stomachs Reviewed

    Kato S, Tanaka A, Kunikata T, Mizoguchi H, and Takeuchi K.

    Alimentary Pharmacology & Therapeutics   Vol. 14 ( s1 ) page: 18-25   2000.4

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  109. Regulatory mechanism of acid secretion in the damaged stomach: role of endogenous nitric oxide Reviewed

    Takeuchi K, Araki H, Kawauchi S, Kunikata T, Mizoguchi H, and Tashima K.

    Journal of Gastroenterology and Hepatology   Vol. 15 ( s1 ) page: 37-45   2000.3

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  110. インドメタシン誘起小腸傷害の発生における一酸化窒素の二面作用 Invited

    田中晶子, 溝口博之, 加藤伸一, 竹内孝治

    Ulcer Research   Vol. 27   page: 176-179   2000

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  111. 一酸化窒素遊離型インドメタシンの小腸傷害性について Invited

    田中晶子, 溝口博之, 鈴木敬三, 加藤伸一, 竹内孝冶

    Cytoprotection & biology   Vol. 8   page: 27-30   2000

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  112. プロスタグランジンEによるインドメタシン誘起胃損傷の抑制: EP受容体サブタイプとの関連 Invited

    鈴木敬三, 荒木秀夫, 溝口博之, 竹内孝治

    Cytoprotection & biology   Vol. 8   page: 31-34   2000

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  113. Protective effect of Irsogladine on monochloramine-induced gastric mucosal lesions in rats: a comparative study with rebamipide Reviewed

    Yamamoto H, Umeda M, Mizoguchi H, Kato S, Takeuchi K.

    World J. Gastroenterol.   Vol. 5 ( 6 ) page: 477-482   1999.12

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    AIM:To examine the effect of irsogladine, a novel antiulcer drug, on the mucosal ulcerogenic response to monochloramine (NH(2)Cl) in rat stomach, in comparison with rebamipide, another antiulcer drug with cytoprotective a ctivity.METHODS AND RESULTS:Oral administration of NH(2)Cl-(120mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs.Both irsogladine (1mg/kg-10mg/ kg,po) and rebamipide (30mg/kg-100mg/kg, po) dose dependently prevented the development of these lesions in response to NH(2)Cl, the effect of irsogladine was significant at 3mg/kg or greater, and that of rebamipide only at 100mg/kg. The protective effect of irsogladine on NH(2)Cl induced gastric lesions was significantly reduced by N( G) nitro L arginine methyl ester (L-NAME) but not by indomethacin, while that of rebamipide was significantly mitigated by indomethacin but not by L-NAME. Topical application of NH(2)Cl-(20mM)caused a marked reduction of potential difference (PD) in exvivo stomachs. This PD reduction was not affected by mucosal application of irso-gladine, but significantly prevented by rebamipide. The mucosal exposure to NH(4)OH (120mM) also caused a marked PD reduction in the ischemic stomach (bleeding from the carotid artery), resulting in gastric lesions. These ulcerogenic and PD responses caused by NH(4)OH plus ischemia were also significantly mitigated by rebamipide, in an indomethacin sensitive manner, while irsogladine potently prevented such lesions without affecting the PD response, in a L-NAME sensitive manner.CONCLUSION:These results suggest that (1)NH(2)Cl gen-erated either exogenously or endogenously damages the gastric mucosa, (2)both irsogladine and rebamipide protect the stomach against injury caused by NH(2)Cl,and (3)the mechanism underlying the protective action of irsogladine is partly mediated by endogenous nitric oxide, while that of rebamipide is in part mediated by endogenous prostaglandins.

  114. Roles of endogenous prostaglandins and nitric oxide in gastroduodenal ulcerogenic responses induced in rats by hypothermic stress Reviewed

    Takeuchi K, Suzuki K, Araki H, Mizoguchi H, Sugamoto S, and Umdeda M.

    Journal of Physiology-Paris   Vol. 93 ( 5 ) page: 423-431   1999.11

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  115. Dual action of nitric oxide in pathogenesis of indomethacin-induced small intestinal ulceration in rats Reviewed

    Tanaka A, Kunikata T, Mizoguchi H, Kato S, and Takeuchi K.

    Journal of Physiology and Pharmacology   Vol. 50 ( 3 ) page: 405-417   1999.9

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  116. Cyclooxygenase-2 selective and nitric oxide-releasing nonsteroidal anti-inflammatory drugs and gastric mucosal responses Reviewed

    Takeuchi K, Suzuki K, Yamamoto H, Araki H, Mizoguchi H, and Ukawa H.

    Journal of Physiology and Pharmacology   Vol. 49 ( 4 ) page: 501-513   1998.12

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Books 2

  1. XIX-N. 麻薬 ニュースタンダード整形外科学

    溝口博之、山田清文( Role: Joint author)

    南江堂  2007.9 

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  2. カプサイシン感受性知覚神経の小腸傷害に対する保護効果-インドメタシン誘起小腸傷害を中心に-胃粘膜防御機構におけるカプサイシン感受性知覚神経の役割-カプサイシンは薬か毒か

    ( Role: Joint author)

    医薬ジャーナル  1999 

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    Language:Japanese

MISC 7

  1. AN OPERANT TASK FOR TESTING RISKY DECISION-MAKING IN MICE

    Wang T, Fukumoto K, Mizoguchi H, Yamada K

    ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH   Vol. 42   page: 48A-48A   2018.8

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)  

  2. Maternal separation as a risk factor for aggravation of neuropathic pain in later life in mice

    Hiroyuki Mizoguchi, Kazuya Fukumoto, Gaku Sakamoto, Shijie Jin, Asako Toyama, Tian Wang, Akio Suzumura, Jun Sato

    Behavioural Brain Research     2018

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:Elsevier B.V.  

    Psychological stresses such as social loss and separation during childhood induce hardship, referred to as emotional pain. These experiences are well-documented risk factors for the development of physical pain in adulthood. However, the underlying neuronal mechanisms of this exacerbation of pain are largely unknown, and consequently there is no effective pharmacotherapy. In this study, we sought to determine whether infant maternal separation (MS) contributes to aggravation of neuropathic pain in adult mice. MS increased anxiety- and depression-like behavioral responses to adult stress. In MS animals, chronic constriction injury (CCI) heightened the sensory dimension of chronic pain relative to that of control mice. However, MS mice treated with fluoxetine for 4 weeks after MS did not exhibit augmentation of allodynia, and their emotional response was attenuated. Microglia were more abundant in the spinal cord in MS/CCI mice than in control/CCI mice. These results suggest that emotional impairment is related to augmentation of neuropathic pain, and that dysfunction of microglial activation contributes to heightened pain sensitivity.

    DOI: 10.1016/j.bbr.2018.06.015

    Scopus

    PubMed

  3. Nicotine and varenicline ameliorate changes in reward-based choice strategy and altered decision-making in methamphetamine-treated rats

    Hiroyuki Mizoguchi, Tian Wang, Mizuki Kusaba, Kazuya Fukumoto, Kiyofumi Yamada

    Behavioural Brain Research     2018

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:Elsevier B.V.  

    Patients suffering from neuropsychiatric disorders such as substance use and addiction disorders show impaired decision-making, which may be associated with their psychiatric disorders. Previously, using a gambling test for rodents, we demonstrated that methamphetamine-dependent rats showed alterations in their decision-making strategy. In this study, we investigated the effect of nicotine on impaired decision-making strategy in rats which have been treated repeatedly with methamphetamine. Nicotine has previously been shown to have therapeutic effects on attentional and cognitive abnormalities in psychosis. Rats were administered methamphetamine subcutaneously (sc) at 4 mg/kg once a day, for 30 days, and their decision-making was then assessed with a rodent gambling task. We found that methamphetamine-treated rats preferred the high-risk/high-return actions, which is consistent with our previous findings. Methamphetamine-induced impairment of decision-making was reversed by daily nicotine treatment (0.3 mg/kg, sc). This effect was associated with the reduction of lose-shift behavior after negative reward prediction error. Repeated treatment with nicotine had no effects on arm-choice behavior in naïve rats. Varenicline, an α4β2-nicotinic acetylcholine receptor partial agonist, also ameliorated the altered decision-making in methamphetamine-treated rats. Our findings suggest that nicotine treatment is useful for ameliorating the altered decision-making caused by methamphetamine treatment, and that the α4β2-nicotinic acetylcholine receptor is a therapeutic target for poor decision-making.

    DOI: 10.1016/j.bbr.2018.06.016

    Scopus

    PubMed

  4. GAP junction/hemichannel blockers ameliorate the disease progression of FTLD/ALS mice

    Takeuchi H, Mizoguchi H, Tanaka F, Suzumura A

    JOURNAL OF THE NEUROLOGICAL SCIENCES   Vol. 381   page: 714-715   2017.10

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    DOI: 10.1016/j.jns.2017.08.2013

  5. Disrupted axon-glia interactions at the paranode in myelinated nerves cause axonal degeneration and neuronal cell death in the aged Caspr mutant mouse shambling. Reviewed

    Takagishi Y, Katanosaka K, Mizoguchi H, Murata Y

    Neurobiology of Aging   Vol. 43   page: 34-46   2016.7

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)  

    DOI: 10.1016/j.neurobiolaging.2016.03.020.

  6. Chronic Hyponatremia Causes Neurologic and Psychologic Impairments Reviewed

    Fujisawa H, Sugimura Y, Takagi H, Mizoguchi H, Takeuchi H, Izumida H, Nakashima K, Ochiai H, Takeuchi S, Kiyota A, Fukumoto K, Iwama S, Takagishi Y, Hayashi Y, Arima H, Komatsu Y, Murata Y, Oiso Y

    Journal of the American Society of Nephrology   Vol. 27 ( 3 ) page: 766-80   2016.3

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)  

    DOI: 10.1681/ASN.2014121196

  7. Insular neural system controls decision-making in healthy and methamphetamine-treated rats Reviewed

    Hiroyuki Mizoguchi, Kentaro Katahira, Ayumu Inutsuka, Kazuya Fukumoto, Akihiro Nakamura, Tian Wang, Taku Nagai, Jun Sato, Makoto Sawada, Hideki Ohira, Akihiro Yamanaka, Kiyofumi Yamada

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   Vol. 112 ( 29 ) page: E3930 - E3939   2015.7

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    Language:English   Publishing type:Rapid communication, short report, research note, etc. (scientific journal)   Publisher:NATL ACAD SCIENCES  

    Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high-reward option more frequently and assigned higher value to high returns than control rats, suggestive of changes in decision-making choice strategy. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-treated animals. Pharmacological studies, together with in vivo microdialysis, showed that the insular neural system played a crucial role in decision-making. Moreover, manipulation of INS activation using designer receptor exclusively activated by designer drug technology resulted in alterations to decision-making. Our findings suggest that the INS is a critical region involved in decision-making and that insular neural dysfunction results in risk-taking behaviors associated with altered decision-making.

    DOI: 10.1073/pnas.1418014112

    Web of Science

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Presentations 180

  1. Dynamic changes in orexin activities in reward-based motivative behavior.

    2022.3.7 

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    Event date: 2022.3

    Language:English   Presentation type:Oral presentation (general)  

  2. 報酬獲得行動に関わる脳内ネットワークの追究

    溝口博之

    2021年度アルコール・薬物依存関連学会合同学術総会  2021.12.18 

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    Event date: 2021.12

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:Web会議(津)  

  3. 依存症がもたらす意思決定異常と脳内報酬系 Invited

    溝口博之、山田清文

    2021年度アルコール・薬物依存関連学会合同学術総会  2021.12.19 

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    Event date: 2021.12

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  4. Activities of orexin neurons in motivative behavior

    Yutao Dong, Hiroyuki Mizoguchi, Akihiro Yamanaka, Kiyofumi Yamada

    2021.6.26 

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    Event date: 2021.6

    Language:English   Presentation type:Oral presentation (general)  

  5. 不確実な状況下における報酬動機づけメカニズムとオレキシン神経活動

    溝口博之

    新学術領域研究 「意志動力学(ウィルダイナミクス)の創成と推進」領域会議  2021.3.17 

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    Event date: 2021.3

    Language:Japanese  

  6. 認知症早期発見と創薬への行動薬理学研究者の挑戦

    溝口博之、山中宏二

    第30回日本医療薬学会年会 

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    Event date: 2020.10 - 2020.11

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

  7. 不確実な状況下における報酬動機づけメカニズムとオレキシン神経活動

    溝口博之

    文科省科研費 新学術領域研究 「意志動力学(ウィルダイナミクス)の創成と推進」領域会議   2020.8.31 

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    Event date: 2020.8 - 2020.9

    Language:Japanese  

  8. 依存症の理解に向けた意思決定の神経回路の解明

    溝口博之、山田清文、山中章弘.

    第43回日本神経科学大会  2020.8.1 

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    Event date: 2020.7 - 2020.8

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

  9. 意思決定異常に対する創薬標的:バレニクリンの有効性.

    溝口博之、山田清文

    第137回日本薬理学会近畿部会  2020.6.20 

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    Event date: 2020.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  10. タッチスクリーン式弁別課題を用いた認知機能解析システムの確立.

    Md.Ali Bin Saifullah, 山中宏二,溝口博之.

    日本薬学会第138年会 

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    Event date: 2018.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  11. リスク下の意思決定における島皮質GABA神経の役割.

    溝口博之,犬束 歩,片平健太郎,山田清文.

    日本アルコール・アディクション医学会学術総会 

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    Event date: 2017.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:横浜   Country:Japan  

  12. 島皮質GABA神経の機能操作は意思決定に影響する

    溝口博之,犬束 歩,片平健太郎,山田清文.

    次世代を担う創薬・医療管理シンポジウム 

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    Event date: 2017.8

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:京都市   Country:Japan  

  13. タッチスクリーン式弁別課題を用いた認知機能解析システムの確立.

    Md.Ali-Bin-Saifullah,溝口博之.

    次世代を担う創薬・医療管理シンポジウム 

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    Event date: 2017.8

    Language:Japanese   Presentation type:Poster presentation  

    Venue:京都   Country:Japan  

  14. 依存性薬物がもたらす認知・意思決定異常

    溝口博之,山田清文

    第40回日本神経科学大会 

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    Event date: 2017.7

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:千葉市   Country:Japan  

  15. ナノボディおよびDARPinを利用したRFP-dependent Creの開発

    犬束 歩,溝口博之,金子涼輔,尾仲達史.

    第40回日本神経科学大会 

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    Event date: 2017.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:千葉   Country:Japan  

  16. 島皮質は薬物依存症モデルラットの意思決定に関与する

    溝口博之,山田清文

    第88 回日本薬理学会 年会 

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    Event date: 2015.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:名古屋   Country:Japan  

  17. DREADD テクノロジーで報酬に基づく意思決定を操作する

    中村旭宏,溝口博之,山田清文

    日本薬学会 第135年会 

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    Event date: 2015.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:神戸   Country:Japan  

  18. 覚せい剤依存症モデルラットの意思決定障害と島皮質

    溝口博之,福本和哉,山田清文

    日本薬学会 第135 年会 

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    Event date: 2015.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:神戸   Country:Japan  

  19. Impaired decision-making in an animal model of methamphetamine dependence.

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    Event date: 2014.12

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  20. 覚せい剤依存ラットの意思決定異常に対するニコチンの効果

    王 天,溝口博之,山田清

    第24 回 日本臨床精神神経薬理 

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    Event date: 2014.11

    Language:Japanese   Presentation type:Poster presentation  

    Venue:名古屋   Country:Japan  

  21. 意思決定異常と島皮質―意思決定研究からみた薬物依存症―

    溝口博之

    日本心理学会第78 回大会 

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    Event date: 2014.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:京都   Country:Japan  

  22. 薬物依存症の意思決定異常と島皮質

    溝口博之,片平健太郎,犬束歩,大平英樹,山中章弘,山田清文

    第36 回日本生物学的精神医学会,第57 回日本神経化学会大会合同年会 

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    Event date: 2014.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:奈良   Country:Japan  

  23. Reward-Based Decision-making in methamphetamine-dependent rat. International conference

    Mizoguchi Hiroyuki, Fukumoto Kazuya, Wang Tian, Yamada Kiyofumi

    9th Federation of European Neuroscience Societies, Forum of Neuroscience 

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    Event date: 2014.7

    Language:English   Presentation type:Poster presentation  

    Country:Italy  

  24. Dysfunction of GABAergic system in the insular cortex is associated with impaired decision-making in methamphetamine-treated rats. International conference

    Yamada Kiyofumi, Fukumoto Kazuya, Wang Tian, Mizoguchi Hiroyuki

    29th CINP World Congress of Neuropsychopharmacology 

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    Event date: 2014.6

    Language:English   Presentation type:Poster presentation  

    Country:Canada  

  25. Decision-making in methamphetamine-dependent rat

    溝口博之,福本和哉,王天,山田清文

    予測と意思 決定の脳内計算機構の解明による人間理解と応用.第7回領域会議 

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    Event date: 2014.6

    Language:Japanese   Presentation type:Poster presentation  

    Venue:北九州   Country:Japan  

  26. DREADD システムと計算論的手法を用いた近視眼的意思決定の追究新学術領域研究

    溝口博之

    予測 と意思決定の脳内計算機構の解明による人間理解と応用.第7回領域会議 

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    Event date: 2014.6

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:北九州   Country:Japan  

  27. 肥満症を想定した食報酬に基づく大脳基底核報酬回路に対する喫煙の効果

    溝口博之

    特定研究「喫 煙と生活習慣病における報酬系の意義」キックオフ会議 

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    Event date: 2014.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京   Country:Japan  

  28. 薬物依存モデル動物の近視眼的意思決定

    溝口博之,福本和哉,王天,佐藤純,山田清文

    第22回神経行動薬理 若手研究者の集い,シンポジウム「次世代に向けての行動薬理学とその新展開」 

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    Event date: 2013.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:福岡   Country:Japan  

  29. Contribution of MMP-9 to pentylenetertrazole-induced kindled seizure by converting pro BDNF to mature BDNF. International conference

    Mizoguchi Hiroyuki, Sato Jun, Sawada Makoto, Nabeshima Toshitaka, Yamada Kiyofumi

    42th Annual Meeting of Society for Nueroscience 

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    Event date: 2012.10

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  30. ニコチンの認知機能改善作用

    山田清文,溝口博之

    平成24年度アルコール・薬物依存関連学会合同学術総会 

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    Event date: 2012.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:札幌   Country:Japan  

  31. Alternation of decision-making behavior is related to the overestimation of risk/benefit values in methamphetamine-treated rats. International conference

    Mizoguchi Hiroyuki, Yamada Kiyofumi

    2012 ISBRA World Congress 

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    Event date: 2012.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  32. 覚せい剤は報酬の利益・損失の評価異常を引き起こす

    溝口博之,山田清文

    第35回日本神経科学大会 

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    Event date: 2012.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:名古屋   Country:Japan  

  33. Increase in cold sensitivity of heart rate in a mouse model of anxiety/depression.

    Sato Jun, Mizutani Yuki, Mizoguchi Hiroyuki, Kodama Koji, Itoh Mariko, Mori Rarami

    The 35th Annual Meeting of the Japan Neuroscience Society 

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    Event date: 2012.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  34. Contribution of MMP-9 to pentylenetertrazole-induced kindled seizure by converting pro BDNF to mature BDNF. International conference

    Yamada Kiyofumi, Mizoguchi Hiroyuki

    FENS 2012 Satellite Event 2nd Annual Conference of COST Action ECMNet 

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    Event date: 2012.7

    Language:English   Presentation type:Oral presentation (general)  

    Country:Spain  

  35. Matrix metalloprotease-9 inhibition improves amyloid β-mediated cognitive impairment and neurotoxicity in mice. International conference

    Mizoguchi Hiroyuki, Tankuma Kazuhiro, Noda Yukihiro, Nabeshima Toshitaka, Yamada Kiyofumi

    Brain Extracellular Matrix in Health and Disease. FENS 2012 Satellite Event 2nd Annual Conference of COST Action EBMNet 

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    Event date: 2012.7

    Language:English   Presentation type:Poster presentation  

    Country:Spain  

  36. Matrix metalloprotease-9 contributes to killed seizure development in pentylenetertrazole-treated mice by converting pro-BDNF to mature BDNF in the hippocampus. International conference

    Mizoguchi Hiroyuki, Sato Jun, Sawada Makoto, Nabeshima Toshitaka, Yamada Kiyofumi

    The 8th FENS Forum of Neuroscience 

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    Event date: 2012.7

    Language:English   Presentation type:Poster presentation  

    Country:Spain  

  37. 脳梗塞におけるmatrix metalloproteinaseとその新たな標的分子としてのneural cell adhesion moleculesの関与

    藤田和歌子,原田慎一,溝口博之,山田清文,鍋島俊隆,徳山尚吾

    第85回日本薬理学会年会,シンポジウム「新しい創薬標的としてのプロテアーゼ依存性シグナルの可能性」 

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    Event date: 2012.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:京都   Country:Japan  

  38. Matrix metalloproteinase-9は成熟型BDNFを増加させることでキンドリング現象に関与する

    溝口博之,佐藤純,山田清文

    第85回日本薬理学会年会,シンポジウム「新しい創薬標的としてのプロテアーゼ依存性シグナルの可能性」 

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    Event date: 2012.3

    Language:English   Presentation type:Oral presentation (general)  

    Venue:京都   Country:Japan  

  39. Matrix metalloproteinase-9 contributes to kindled seizure development in pentylenetetrazole-treated mice by converting pro-BDNF to mature BDNF in the hippocampus.

    第4回NAGOYAグローバルリトリート 

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    Event date: 2012.2

    Language:English   Presentation type:Oral presentation (general)  

    Venue:名古屋   Country:Japan  

  40. 報酬に基づく意思決定機構に対する覚せい剤の効果

    溝口博之

    グローバルCOE第29回プログレスレポート会議 

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    Event date: 2012.2

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:名古屋   Country:Japan  

  41. 報酬に基づく意思決定に対するmethamphetamineの影響

    溝口博之,福本和哉,佐藤純,山田清文

    第120回日本薬理学会近畿部会 

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    Event date: 2011.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:京都   Country:Japan  

  42. 報酬に基づく意思決定機構に対する覚せい剤の効果

    溝口博之,佐藤純,山田清文

    第21回日本臨床精神神経薬理学会,第41回日本神経精神薬理学会合同年会 

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    Event date: 2011.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  43. 報酬に基づく意思決定機構に対する覚せい剤の効果

    溝口博之,佐藤純,山田清文

    平成23年度アルコール・薬物依存関連学会合同学術総会 

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    Event date: 2011.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:名古屋   Country:Japan  

  44. マトリックスメタロプロテアーゼは成熟型BDNFを増加させることでキンドリング現象に関与する

    溝口博之,佐藤純,澤田誠,鍋島俊隆,山田清文

    第45回日本てんかん学会 

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    Event date: 2011.10

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  45. Matrix metalloproteinase-9 contributes to kindled seizure development in pentylenetetrazole-treated mice by converting pro-BDNF to mature BDNF in the hippocampus.

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    Event date: 2011.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  46. 覚せい剤依存および認知障害についての行動学的基礎研究

    溝口博之,山田清文

    日本動物心理学会第155回例会 

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    Event date: 2011.3

    Language:Japanese   Presentation type:Poster presentation  

    Venue:名古屋   Country:Japan  

  47. 意思決定の行動学的解析:放射状迷路を用いた小動物用ギャンブルテスト

    溝口博之,福本和哉,Erika Toth,佐藤純,山田清文

    第118回日本薬理学会近畿部会 

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    Event date: 2010.11

    Language:Japanese   Presentation type:Poster presentation  

    Venue:豊中   Country:Japan  

  48. Therapeutic potential of nicotine for methamphetamine-induced impairment of sensorimotor gating: Involvement of pallidotegmental neurons. International conference

    Mizoguchi, H., Arai, S., Koike, H., Ibi, D., Nagai, T., Kamei, H., Nabeshima, T., Kim, HC., Takuma, K. and Yamada, K.

    Neuroscience 2010 

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    Event date: 2010.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  49. 寒冷ストレスによる気分障害および慢性痛モデルラットの血中ノルアドレナリン量の変化

    佐藤純,大藪竜昇,溝口博之,大和恵子

    第49回日本生気象学会大会 

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    Event date: 2010.11 - 2011.11

    Language:Japanese   Presentation type:Poster presentation  

    Venue:東京   Country:Japan  

  50. ラットを用いた意思決定の行動学的解析:放射状迷路を用いた小動物用ギャンブリングテスト

    溝口博之,福本和哉,トスエリカ,佐藤純,山田清文

    平成22年度アルコール・薬物依存関連学会合同学術総会 

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    Event date: 2010.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:北九州   Country:Japan  

  51. ストレス誘発性抑うつモデルマウスにみられる神経障害性疼痛の増強 International conference

    大宮康次郎,溝口博之,佐藤純

    第32回日本疼痛学会 

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    Event date: 2010.7

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  52. 神経性疾患におけるマトリックスメタロプロテアーゼの動態と機能解析

    溝口博之

    第5回名古屋大学環境医学研究所・生理学研究所合同シンポジウム 

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    Event date: 2010.1

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:岡崎   Country:Japan  

  53. 遺伝子ー環境相互作用に基づく統合失調症モデルマウスの作製

    衣斐大祐, 永井拓, 溝口博之, 北原裕子, 小池宏幸, 新田淳美, 米田幸雄, 澤明, 鍋島俊隆, 山田清文

    日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会 

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    Event date: 2009.11

    Language:Japanese   Presentation type:Poster presentation  

    Venue:四日市   Country:Japan  

  54. Pharmacological treatment with nicotine on methamphetamine-induced impairment of sensorimotor gating.

    Mizoguchi, H., Arai, S., Koike, H., Ibi, D., Nagai, T., Kamei, H., Nabeshima, T., Kim, H-C., Takuma, K. and Yamada, K.

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    Event date: 2009.11

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  55. 気圧低下曝露がラットの抑うつ行動に与える影響

    深谷佳乃子,溝口博之,佐藤純

    第48回日本生気象学会大会 

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    Event date: 2009.10

    Language:Japanese   Presentation type:Poster presentation  

    Venue:つくば   Country:Japan  

  56. 動物の行動から脳の働きを探る

    溝口博之

    名古屋大学第5回ホームカミングデイ市民公開講座「脳の機能の不思議」 

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    Event date: 2009.10

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Venue:名古屋   Country:Japan  

  57. Involvement of matrix metalloprotease-9 in cognitive impairment and neurotoxicity induced by i.c.v. injection of amyloid βprotein in mice. International conference

    39th Annual Meeting of Society for Neuroscience 

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    Event date: 2009.10

    Language:English   Presentation type:Poster presentation  

    Venue:Chicago   Country:United States  

  58. 名古屋大学環境医学研究所実験動物飼育施設における施設管理体制の確立

    森ララミ,伊藤麻里子,加納安彦,溝口博之,佐藤純

    第43回日本実験動物技術者協会総会 

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    Event date: 2009.10

    Language:Japanese   Presentation type:Poster presentation  

    Venue:新潟   Country:Japan  

  59. Loweing barometric pressure aggravates anxiety/depression-like behavior in rats.

    Sato, J., Fukaya, K. and Mizoguchi, H.

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    Event date: 2009.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  60. Beneficial treatment of nicotine in methamphetamine (METH)-induced impairment of sensorimotor gating.

    Mizoguchi, H., Ibi, D., Kamei, H., Nabeshima, T., Kim, H-C., Takuma, K. and Yamada, K.

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    Event date: 2009.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  61. CpG-activatid microglia reduce oligomeric amyloid β neurotoxicity in vitro and ameliorate memory deficit in mouse models of Alzheimer's disease.

    Doi, Y., Mizuno, T., Mizoguchi, H., Takeuchi, H. and Suzumura, A.

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    Event date: 2009.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  62. Involvement of matrix metalloproteinase-9 in the development of pentylenetetrazole-induced kindled seizure in mice. International conference

    Mizoguchi, H., Nakade, J., Ibi, D., Someya, E., Koike, H., Kamei, H., Nabeshima, T., Itohara, S., Takuma, K. and Yamada, K.

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    Event date: 2009.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  63. アミロイド蛋白により誘発される記憶障害におけるMatrix metalloproteinasesの役割

    溝口博之,田熊一敞,衣斐大祐,アルカム トルソン,毛利彰浩,野田幸弘,鍋島俊隆,山田清文

    第115回日本薬理学会近畿部会 

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    Event date: 2009.6

    Language:Japanese   Presentation type:Poster presentation  

    Venue:金沢   Country:Japan  

  64. 周産期における免疫異常は思春期マウスにおける情動および認知機能を障害する

    永井拓,衣斐大祐,溝口博之,鍋島俊隆,山田清文

    第2回次世代を担う若手医療薬科学シンポジウム 

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    Event date: 2008.12

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  65. GABAB receptor agonist baclofen improves cognitive deficit induced by repeated methamphetamine treatment in mice International conference

    Yamada, K., Mizoguchi, H., Arai, S., Nagai, T., Ibi, D., Kamei, H. and Takuma, K

    38th Annual Meeting of Society for Neuroscience 

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    Event date: 2008.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  66. A novel molecule ''shati'' inhibits methamphetamine-induced hyperlocomotion, sensitization, and conditioned place preference via tumor necrosis factor-α. International conference

    Niwa, M., Nitta, A., Mizoguchi, H., Itoh, Y., Noda, Y., Nagai, T., Ozaki, N. and Nabeshima, T.

    38th Annual Meeting of Society for Neuroscience 

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    Event date: 2008.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  67. The extensive nitration of neurofilament light chain in the hippocampus contributes to the cognitive impairment in mice. International conference

    Alkam, T., Nitta, A., Mizoguchi, H., Itoh, A., Yamada, K. and Nabeshima, T.

    38th Annual Meeting of Society for Neuroscience 

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    Event date: 2008.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  68. 周産期におけるウィルス感染が精神機能発達および統合失調症関連遺伝子発現に及ぼす影響

    衣斐大祐,永井拓,溝口博之,田熊一敞,北原裕子,小池宏幸,日比(古川)陽子,新田淳美,米田幸雄,山田清文

    衣斐大祐,永井拓,溝口博之,田熊一敞,北原裕子,小池宏幸,日比(古川)陽子,新田淳美,米田幸雄,山田清文 

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    Event date: 2008.10

    Language:Japanese   Presentation type:Poster presentation  

    Venue:東京   Country:Japan  

  69. The extensive nitration of neurofilament light chain in the hippocampus is associated with the cognitive impairment induced by amyloid B in mice.

    Alkam, T., Nitta, A., Mizoguchi, H., Itoh, A., Murai, R., Nagai, T., Yamada, K., Nabeshima, T.

    International Symposium on Brain Development and Neuropsychiatric Disorders 

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    Event date: 2008.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  70. Development of schizophrenia-like behaviors and susceptibility gene expression in a viral infection model during perinatal stage.

    Ibi, D., Nagai, T., Mizoguchi, H., Nitta,A., Takuma, K., Yamada, K.

    International Symposium on Brain Development and Neuropsychiatric Disorder 

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    Event date: 2008.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  71. Activation of postsynaptic dopamine D1 receptors promotes the release of tissue plasminogen activator in the nucleus accumbens via PKA signaling.

    Nagai, T., Ito, M., Mizoguchi, H., Kim, H., Nabeshima, T., Yamada, K.

    International Symposium on Brain Development and Neuropsychiatric Disorders 

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    Event date: 2008.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  72. 覚せい剤誘発認知障害におけるGABAB受容体アゴニストの効果

    溝口博之,永井拓,山田清文

    第11回ニコチン・薬物依存研究フォーラム(平成20年度アルコール・薬物依存関連学会合同年会) 

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    Event date: 2008.9

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  73. 統合失調症様認知障害モデル動物におけるGABAB受容体作用薬の有効性

    溝口博之,山田清文

    第51回日本神経化学会 

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    Event date: 2008.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  74. アミロイドβタンパク質の神経細胞膜輸送におけるRAGEおよびp38MAPKの役割

    田熊 一敞,溝口博之,STERN David M,山田清文,YAN Shi Du

    第51回日本神経化学会 

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    Event date: 2008.9

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  75. Aβ処置マウス海馬でのニューロフィラメントLが過剰にニトロ化されると認知障害が誘導される

    ALKAM Tursun,新田淳美,溝口博之,伊東亜紀夫,山田清文,鍋島俊隆

    第51回日本神経化学会 

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    Event date: 2008.9

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  76. Cognitive impairment in a mouse model of viral infection during perinatal stage

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    Event date: 2008.7

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  77. ニコチンのドパミン遊離作用におけるプロテアーゼシグナルの役割

    山田清文,永井拓,田熊一敞,溝口博之,鍋島俊隆

    財団法人喫煙科学研究財団第23回平成19年度助成研究発表会 

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    Event date: 2008.7

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  78. Restraining tumor necrosis factor-alpha by thalidomide prevents the Amyloid beta-induced impairment of recognition memory in mice

    Alkam, T., Nitta, A., Mizoguchi, H., Saito, K., Seshima, M., Itoh, A., Yamada, K. and Nabeshima, T

    第113回日本薬理学会近畿部会 

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    Event date: 2008.6

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  79. 名古屋大学環境医学研究所実験動物飼育施設における研究支援体制

    伊藤麻里子,武井明彦,森ララミ,加納安彦,溝口博之,佐藤純

    日本実験動物科学技術 

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    Event date: 2008.5

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  80. 遺伝子変異マウスを用いた薬物依存モデルの行動解析

    山田清文, YAN Yijin,永井拓,溝口博之,新田淳美,鍋島俊隆

    (シンポジウム「精神疾患とその病態モデル小動物の表現型解析」)第55回日本実験動物学会総会, 第42回日本実験動物技術者協会総会合同大会 

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    Event date: 2008.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  81. 閉経後認知障害モデルラットに対するイチョウ葉エキス(EGb761)の効果

    舩津瑤子, 田熊一敞, 保科有希, 姫野友紀子, 新井佐和子, 松尾亜伊, 永井拓, 溝口博之, 亀井 浩行, 小池浩司, 井上正樹, 山田清文

    第 10 回日本補完代替医 療学会学術集会 

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    Event date: 2007.11

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  82. Strogen attenuates chronic restraint stress-induced hippocampal neuronal loss and cognitive dysfunction in ovariectomized rats International conference

    Takuma, K., Matsuo, A., Hoshina, Y., Himeno, Y., Arai, S., Kamei, H., Mizoguchi, H., Nagai, T., Koike, K., Inoue, M. and Yamada, K.

    The 37th Annual meeting Society for Neuroscience 

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    Event date: 2007.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  83. Histone modification in methamphetamine-associated contextual memory

    Mizoguchi, H., Takuma, K., Ibi, D., Someya, E., Nagai, T., Yijan, Y., Kanou, Y., Nabeshima, T., Sawada, M., Sato, J. and Yamada, K

    The 81st Annual Meeting of the Japanese Pharmacological Society 

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    Event date: 2007.11

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  84. Effects of single and repeated administration of methamphetamine or morphine on neuroglycan C gene espression in the rat brain International conference

    Nitta, A., Ishikawa, K., Mizogushi, H., Mouri, A., Murai, R., Miyamoto, Y., Noda, Y., Kitaichi, K., Yamada, K. and Nabeshima, T

    The 37th Annual meeting Society for Neuroscience 

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    Event date: 2007.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  85. A natural scavenger of peroxynitrite, rosmarinic acid, protects against impairment of memory induced by Abeta(23-35) International conference

    Alkam, T., Nitta, A., Mizoguchi, H., Itoh, A., Nabeshima, T., Neuropsychopharmacol. & Hosp., Nagoya Univ. Grad Sch. Med., Nagoya, Japan, Col. of Traditional Uighur Med., Hotan, China, Japanese Drug Organization of Appropriate Use and Res., Nagoya, Japan

    The 37th Annual meeting Society for Neuroscience 

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    Event date: 2007.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  86. Clozapine and agonists for glycine modulatory site of NMDA receptor prevent a decrease in neurogenesis in mice repeatedly treated with phencyclidine International conference

    Yamada,K., Maeda, K., Sugino, H., Hirose, T., Kitagawa, H Nagai, T., Mizoguchi, H. and Takuma, K

    The 37th Annual meeting Society for Neuroscience 

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    Event date: 2007.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  87. Involvement of tissue plasminogen activator in the development of behavior and neurochemical sensitization induced by repeated treatment with methamphetamine. International conference

    Fukakusa, A., Nagai, T., Mizoguchi, H., Nabeshima, T., Takuma, K. and Yamada, K

    The 37th Annual meeting Society for Neuroscience 

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    Event date: 2007.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  88. Implication of the pallidotegmental neurons in methamphetamine- and MK-801-induced disruption of prepulse inhibition of the startle response in mice. International conference

    Arai,S., Mizoguchi, H., Nagai, T., Takahashi, K., Kamei, H., Takuma, K. and Tamada, K

    The 37th Annual meeting Society for Neuroscience 

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    Event date: 2007.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  89. Social isolation rearing-induced deficits in spatial memory and emotion is accompanied by the impairment of neurogenesis in the hippocampus. International conference

    Ibi, D., Takuma, K., Koike, H., Kamei, H., Mizoguchi, H. and Yamada, K

    The 37th Annual meeting Society for Neuroscience 

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    Event date: 2007.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  90. Reduction of methamphetamine-induced sensitization and reward, but not cognitive impairment, in matrix metalloproteinase-2 and -9 deficient mice. International conference

    Mizoguchi, H., Yamada, K., Niwa, M., Mouri, A., Mizuno, T., Noda, Y., Nitta, A., Itohara, S., Banno, Y. and Nabeshima, T

    The 37th Annual meeting Society for Neuroscience 

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    Event date: 2007.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  91. 更年期障害モデル動物の記憶障害に対するコリンエステラーゼ阻害薬の改善効果

    船津瑶子,田熊 一敞,福崎笑子,姫野友紀子,北原裕子,保科有希,亀井浩行,溝口博之,永井拓,小池浩司,井上正樹,山田清文

    第17回日本医療薬学会年会 

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    Event date: 2007.9

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  92. Role for tissue plasminogen activator in methamphetamine-induced reward, sensitization and cognitive impairment in mice

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    Event date: 2007.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  93. メタンフェタミン連続投与による異常行動とマトリクスメタロプロテアーゼの生理活性変化

    溝口博之, 山田清文, 丹羽美苗, 毛利彰宏, 野田幸裕, 新田淳美, 糸原重美, 坂野喜子, 鍋島俊隆

    第19回日本アルコール精神医学会、第10回ニコチン・薬物依存研究フォーラム合同学術総会 

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    Event date: 2007.9

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  94. マウスの幼若期長期隔離飼育による海馬神経新生の低下と認知・情動・異常の発現

    衣斐大祐,田熊一敞,小池宏幸,溝口博之,山田清文

    生体機能と創薬シンポジウム 

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    Event date: 2007.9

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  95. 閉経後モデルマウスの記憶障害に対するコリンステラーゼ阻害薬の効果

    船津瑶子, 田熊 一敞, 姫野友紀子, 福崎笑子, 北原裕子, 保科有希, 亀井浩行, 溝口博之, 永井拓,小池浩司, 井上正樹, 山田清文

    生体機能と創薬シンポジウム 

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    Event date: 2007.9

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  96. Matrix metalloproteinase-9はpentylenetetrazole誘発性キンドリングの形成に関与する

    中出順也, 溝口博之, 橘正毅, 糸原重美, 鍋島 俊隆, 田熊 一敞, 山田 清文

    生体機能と創薬シンポジウム 

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    Event date: 2007.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  97. 統合失調症モデル動物のプレパルス抑制障害における淡蒼球‐下橋網様核神経の関与

    新井佐和子,溝口博之,永井拓,亀井浩行,田熊一敞,山田清文

    生体機能と創薬シンポジウム 

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    Event date: 2007.9

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  98. A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Abeta (25-35)

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    Event date: 2007.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  99. Implication of matrix metalloprotease-9 in cognitive impairment induced by i.c.v. injection of Aβ in mice

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    Event date: 2007.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  100. Implication of matrix metalloproteinase-9 in cognitive impairment induced by i.c.v. injection of Aβ in mice

    Mizoguchi, H., Takuma, K., Fukuzaki, E., Ibi, D., Akita, F., Someya, E., Alkam, T., Tsunekawa, H., Mouri, A., Noda, Y., Nabeshima, T., Yamada, K

    Neuro2007 Satellite Symposium 

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    Event date: 2007.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  101. Implication of the pallidotegmental neurons in methamphetamine-and MK-801-induced impairment of prepulse inhibition of the startle reflex in mice.

    Arai, S., Mizoguchi, H., Nagai, T., Takahashi, K., Kamei, H., Takuma, K.

    Neuro2007 

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    Event date: 2007.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  102. Social isolation rearing impairs neurogenesis and behavioral development.

    IBI, D., Takuma, K., Koike, H., Mizoguchi, H., Yamada, K.

    Neuro2007 

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    Event date: 2007.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  103. Role of recepter for advanced glycation end products in neuronal uptake of amyloid β-peptide

    Fukuzaki, E., Takuma, K., Mizoguchi, H., Stern, D, M., Yan, S, S., Yamada, K.

    Neuro2007 

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    Event date: 2007.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  104. Role for tPA in the development of sensitization for methamphetamine-induced dopamine release

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    Event date: 2007.7

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  105. 組織プラスミノーゲン活性化因子による依存性薬物の報酬効果の制御.(シンポジウム6「薬物依存‐臨床応用への可能性」)

    永井拓, 田熊一敞, 溝口博之, 鍋島俊隆, 山田清文

    第29回日本生物学的精神医学会・第37回日本神経精神薬理学会合同年会 

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    Event date: 2007.7

    Language:Japanese  

    Country:Japan  

  106. Oral vaccination with a viral vector attenuates memory deficits in a mouse Alzheimer model

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    Event date: 2007.7

    Language:English   Presentation type:Oral presentation (general)  

  107. Implication of matrix metalloproteinase-9 in the development of kindling in mice

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    Event date: 2007.7

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  108. ラットにおけるmethamphetamine誘発空間作業記憶障害に対するnicotineの効果

    溝口博之, 衣斐大祐, 高瀬文超, 永井拓, 田熊一敞, 山田清文

    第29回日本生物学的精神医学会・第37回日本神経精神薬理学会合同年会 

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    Event date: 2007.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  109. Social isolation rearing reduces neurogenesis leading to memor deficit in mice

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    Event date: 2007.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  110. アダプター蛋白複合体μ3Bサブユニット欠損マウスの移動に対するGABA作動薬,fluoxetineおよびnisoxetineの効果

    小池宏幸,田熊一敞,永井拓, 溝口博之,衣斐大祐, 中津 史,大野博司,山田清文

    第111回日本薬理学会近畿部会 

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    Event date: 2007.6

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  111. Involvement of matrix metalloproteinase-9 in the pentylenetetrazole-induced kindled seizure in mice

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    Event date: 2007.3

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  112. 統合失調症の認知障害モデル.(シンポジウム24「精神疾患治療の基礎から臨床へ」)

    山田清文, 田熊一敞, 溝口博之, 永井拓, 亀井浩行, 野田幸裕, 鍋島俊隆

    日本薬学会第127年会 

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    Event date: 2007.3

    Language:Japanese  

    Country:Japan  

  113. Role of the tPA-plasmin-PAR1 signaling in nicotine rewards

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    Event date: 2007.3

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  114. Role of dopamine D1 receptor/ERK1/2 signal in protein synthesis-dependent long-term recognition memory

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    Event date: 2007.3

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  115. Reduction of methamphetamine-induced sensitization and reward in matrix metalloproteinase-2 and-9 deficient mice

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    Event date: 2007.3

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  116. Minocycline improves the object recognition impairment induced by repeated methamphetamine treatment in mice

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    Event date: 2007.3

    Language:English  

    Country:Japan  

  117. アミロイドβタンパク注入マウスにおけるマトリックスメタロプロテアーゼの動態変化とその機能解析

    溝口博之, 田熊一敞, 衣斐大祐, 秋田史生, アルカムトルソン, 恒川浩子, 毛利彰宏, 野田幸裕, 鍋島俊隆, 山田清文

    第16回神経行動薬理若手研究者の集い 

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    Event date: 2007.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  118. メタンフェタミン誘発性行動障害におけるマトリックスメタロプロテアーゼの動態変化:細胞外ドパミン遊離量の調節

    溝口博之, 山田清文, 丹羽美苗, 毛利彰宏, 野田幸裕, 新田淳美, 糸原重美, 坂野喜子, 鍋島俊隆

    第17回マイクロダイアリシス研究会 

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    Event date: 2006.12

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  119. 組織プラスミノーゲン活性化因子によるメタンフェタミン誘発性ドパミン遊離の増強

    深草亜由美, 永井拓, 溝口博之, 鍋島俊隆, 田熊一敞, 山田清文

    日本薬学会北陸支部第115回例会 

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    Event date: 2006.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  120. てんかんモデル動物におけるMatrix Metalloproteinase-9の動態と機能解析

    中出順也, 溝口博之, 深草亜由美, 田熊一敞, 鍋島俊隆, 山田清文

    日本薬学会北陸支部第115回例会 

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    Event date: 2006.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  121. TNF-α is required for protein nitration induced by Aβ. International conference

    Alkam, T., Nitta, A., Mizoguchi, H., Saito, K., Seishima, M., Itoh, A. and Nabeshima, T.

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    Event date: 2006.10

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  122. Targeting the tPA-plasmin-protease activated receptor-1 system for the treatment of nicotine dependence. (Symposium 2”New aspects of cell signaling”) International conference

    Ito, M., Nagai, T., Nakamichi, N., Mizoguchi, H., Kamei, H., Fukakusa, A., Takuma, K., Nabeshima, T. and Yamada, K

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    Event date: 2006.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  123. ネプリライシンの阻害によるAβの蓄積と学習障害

    毛利彰宏, 野田幸裕, 岩田修永, 西道隆臣, Li-Bo ZOU, Dayong WANG, Min-Wei WANG, 溝口博之, 鍋島俊隆

    第12回日本行動薬理研究会 

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    Event date: 2006.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  124. メタンフェタミン連続投与による異常行動とマトリクスメタロプロテアーゼの生理活性変化

    溝口博之, 山田清文, 丹羽美苗, 毛利彰宏, 野田幸裕, 新田淳美, 糸原重美, 坂野喜子, 鍋島俊隆

    第12回日本行動薬理研究会 

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    Event date: 2006.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  125. Aβ impairs memory in mice via tumor necrosis factor-α

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    Event date: 2006.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  126. MMP-2/9 deficient mice show reduced responses to METH in behavioral changes and dopamine release

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    Event date: 2006.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  127. TNF-α is critically involved in the onset of Aβ-induced memory impairment

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    Event date: 2006.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  128. メタンフェタミン連続投与により誘発されるドパミン遊離増強におけるtPA-plasmin系の関与

    生体機能と創薬シンポジウム2006 

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    Event date: 2006.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  129. アルツハイマーモデルラットにおける咀嚼機能と海馬からの神経伝達物質遊離との関連性

    串田祥生, 木本克彦, 堀紀雄, 溝口博之, 新田淳美, 鍋島俊隆, 豊田實

    第115回日本補綴歯科学会学術大会 

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    Event date: 2006.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  130. Involvement of ERK1/2 signaling pathway in seeking behaviors induced by methamphetamine in place preference and self-administration. (Sympojium) International conference

    RIKEN Brain Science Institute One-Day Workshop “Topics in Reward and Addiction" 

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    Event date: 2006.3

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  131. Rosmarinic acid protects against memory impairments induced by acute i.c.v. injection of Aβ25-35

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    Event date: 2006.3

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  132. 覚醒剤およびNMDAによる精神障害の発現の分子機序

    野田幸裕, 鍋島俊隆, 毛利彰宏, 森瀬貴子, 溝口博之, 新田淳美, 北市清幸, 岩村樹憲

    厚生労働科学研究費補助金(医薬品・医療機器等レギュラトリーサイエンス総合研究推進事業)研究「依存性薬物および未規制薬物による神経毒性と精神病の発現機序に関する研究」平成17年度班会議 

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    Event date: 2006.2

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  133. The allosteric potentiation of nicotinic acetylcholine receptors by galantamine ameliorates the cognitive dysfunction in the amyloid β- treated mice: Involvement of dopaminergic systems International conference

    44th Annual Meeting of American College of Neuropsychopharmacology 

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    Event date: 2005.12

    Language:English   Presentation type:Oral presentation (general)  

  134. Tissue plasminogen activator (tPA) knock-out mice overrespond to morphine self-administration mediated by dopamine D1 receptor International conference

    35th Annual Meeting of Society for Neuroscience 

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    Event date: 2005.11

    Language:English   Presentation type:Oral presentation (general)  

  135. Reinstatement of methamphetamine-seeking behavior in C57BL/6J mice demonstrated by intravenous self-administration International conference

    35th Annual Meeting of Society for Neuroscience 

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    Event date: 2005.11

    Language:English   Presentation type:Oral presentation (general)  

  136. Regulation of methamphetamine reward by ERK1/2Elk-1 signaling pathway via the activation of dopamine receptors. International conference

    Taiwan-Japan Joint Seminar 

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    Event date: 2005.8

    Language:English   Presentation type:Oral presentation (general)  

  137. Relapse of METH dependence in C57BL/6J mice demonstrated by reinstatement of self-administration

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    Event date: 2005.7

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  138. メタンフェタミン連続投与による脳内ニューログリカンCの発現変化

    石川和宏, 新田淳美, 溝口博之, 毛利彰宏, 村井里菜, 宮本嘉明, 野田幸裕, 北市清幸, 山田清文, 鍋島俊隆

    第51回日本薬学会東海支部総会・大会 

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    Event date: 2005.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  139. Effects of single and repeated administration of methamphetamine or morphine on neuroglycan C gene expression in the rat brain International conference

    8th World Congress of Biological Psychiatry 

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    Event date: 2005.6

    Language:English   Presentation type:Oral presentation (general)  

  140. The brain areas related to methamphetamine dependence in rats(symposium047 “Molecular Mechanism of Neurotoxicity and Psychosis Induced by Methamphetamine International conference

    8th World Congress of Biological Psychiatry 

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    Event date: 2005.6

    Language:English   Presentation type:Oral presentation (general)  

  141. The regulation of MMP/TIMP system on the sensitization induced by methamphetamine through the dopamine signaling in the rat

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    Event date: 2005.3

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  142. オピオイド系鎮痛薬と精神刺激薬に共通した依存形成の神経機構に関する研究‐治療薬の開発を目指して‐.(シンポジウム2)

    新田淳美, 溝口博之, 丹羽美苗, Yan Yijin, 山田裕一郎, 山田清文, 坂野喜子, 斉藤邦明, 清島満, 野田幸裕, 鍋島俊隆

    文部科学省目標達成型脳科学研究「依存性薬物により誘発される精神障害の機構の解明の研究」平成16年度後期研究報告会 

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    Event date: 2005.3

    Language:Japanese   Presentation type:Oral presentation (general)  

  143. ラットにおけるメタンフェタミン誘発細胞外ドーパミン量の増大に対する MMP/TIMP の調節機構

    溝口博之, 山田清文, 丹羽美苗, 毛利彰宏, 新田淳美, 野田幸裕, 坂野喜子, 鍋島俊隆

    第8回ニコチン・薬物依存研究フォーラム学術年会 

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    Event date: 2005.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  144. Tissue plasminogen activator (tPA) knockout mice over-respond to morphine self-administration mediated by dopamine D1 receptor

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    Event date: 2005.3

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  145. ドーパミン受容体の活性化を介したERK1/2/Elk-1 シグナルによるメタンフェタミンの報酬効果の調節

    第8回ニコチン・薬物依存研究フォーラム学術年会 

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    Event date: 2005.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  146. オピオイド系鎮痛薬と精神刺激薬に共通した依存形成の神経機構に関する研究‐治療薬の開発を目指して‐.(シンポジウム2)

    新田淳美, 溝口博之, 丹羽美苗, Yan YIJIN, 山田裕一郎, 山田清文, 坂野喜子, 斉藤邦明, 清島満, 野田幸裕, 鍋島俊隆

    文部科学省目標達成型脳科学研究「依存性薬物により誘発される精神障害の機構の解明の研究」平成16年度前期研究報告会 

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    Event date: 2004.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  147. The MMP/TIMP system is involved in the sensitization induced by Methamphetamine in the rat

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    Event date: 2004.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  148. Tissue plasminogen activator(t-PA) is involved in morphine-induced rewarding effects

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    Event date: 2004.7

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  149. メタンフェタミン誘発行動障害におけるMatrix metalloproteinase (MMP) / Tissue inhibitor of Matrix metalloproteinase (TIMP) システムの関与

    第105回日本薬理学会近畿部会 

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    Event date: 2004.6

    Language:Japanese  

    Country:Japan  

  150. Tissue plasminogen activator (t-PA) is involved in morphine-induced rewarding effects

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    Event date: 2004.5

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  151. Tissue plasminogen activator (tPA) is involved in morphine-induced rewarding effects in mice

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    Event date: 2004.2

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  152. メタフェタミン誘発行動障害におけるMatrix metalloproteinases(MMP)/ Tissue inhibitor of Matrix metalloproteinase(TIMP)システムの関与

    溝口博之, 毛利彰宏, 丹羽美苗, 水野朋子, 山田清文, 野田幸裕, 新田淳美, 鍋島俊隆

    第1回21世紀COE若手研究発表会「名古屋大学発のブレイクスルーをめざして 

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    Event date: 2004.2

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  153. Effects of single and repeated administration of methamphetamine and morphine on neurolgycan C gene expression in the rat brain International conference

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    Event date: 2003.8

    Language:English   Presentation type:Oral presentation (general)  

  154. Involvement of tissue inhibitor of metallo-proteinase-2 in the brain of methamphetamine dependent rat International conference

    International Society for Neurochemistry/Asian Pacific Society for Neurochemistry Sponsored Satellite Meeting 

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    Event date: 2003.7

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  155. The role of neuroglycan C on the sensitization induced by methamphetamine (MAP) in rat

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    Event date: 2003.7

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  156. ラットにおけるメタンフェタミン連続投与によるneuroglycan C の発現変化

    溝口博之, 石川和宏, 山田清文, 内山武久, 吉村正子, 宮本嘉明, 新田淳美, 鍋島俊隆

    第103回日本薬理学会近畿部会 

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    Event date: 2003.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  157. メタンフェタミン依存動物に認められる神経精神行動障害の形成機序‐遺伝子変異マウスを用いたアプローチ.(シンポジウム12「薬物依存症の神経科学:現状での問題点と依存形成機構解明へのアプローチ」)

    野田幸裕, 溝口博之, 永井拓, 新田淳美, 鍋島俊隆

    日本薬学会第123年会 

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    Event date: 2003.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  158. Increase of tissue inhibitor of metalloproteinase-2 contents in the brain of methamphetamine dependent rat

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    Event date: 2003.3

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  159. オピオイド系鎮痛薬と神経刺激薬に共通した薬物依存の形成機構.科学技術振興調整費目標達成脳科学研究「依存性薬物により誘発される精神障害の機構の解明の研究」

    平成14年度班会議 

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    Event date: 2003.2

    Language:Japanese  

    Country:Japan  

  160. メタンフェタミン誘発精神依存におけるERKの関わりについて

    溝口博之, 水野誠, 水野朋子, 山田清文, 新田淳美, 鍋島俊隆

    第102回日本薬理学会近畿部会 

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    Event date: 2002.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  161. Methamphetamine投与ラット脳内におけるTissue Inhibitor of Metalloprotainase-2(TIM-2)の発現変化

    水野朋子, 山田清文, 溝口博之, 石川和宏, 宮本嘉明, 吉村正子, 内山武久, 新田淳美, 鍋島俊隆

    第32回日本神経精神薬理学会年会 

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    Event date: 2002.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  162. モルヒネ依存形成におけるtissue plasminogen activatorの関与

    永井拓, 山田清文, 石川和宏, 宮本嘉明, 吉村正子, 水野朋子, 溝口博之, 新田淳美, 野田幸裕, 鍋島俊隆

    第32回日本神経精神薬理学会年会 

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    Event date: 2002.10

    Language:Japanese  

    Country:Japan  

  163. メタンフェタミン誘発条件付け場所嗜好性試験の発現に関わる神経シグナル伝達

    溝口博之, 水野誠, 水野朋子, 内山武久, 吉村正子, 山田清文, 新田淳美, 鍋島俊隆

    第32回日本神経精神薬理学会年会 

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    Event date: 2002.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  164. Effect of nefiracetam on discriminative stimulus effects of morphine in rats International conference

    Mizoguchi, H., Uchiyama, T., Nakajima, A., Mizuno, T., Noda, Y., Yamada, K. and Nabeshima, T

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    Event date: 2002.10

    Language:English   Presentation type:Oral presentation (general)  

  165. イムノフィリンリガンドの神経栄養因子産生誘導を介したアセチルコリン含量増加による神経保護効果

    新田淳美, 野田幸裕, 溝口博之, 鍋島俊隆, 古川昭栄

    第6回神経伝達物質研究会 

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    Event date: 2002.8

    Language:Japanese  

    Country:Japan  

  166. ラットにおけるMorphine誘発Tissue Inhibitor of Matrix Metalloproteinase-2 mRNAの発現変化

    溝口博之, 内山武久, 吉村正子, 水野朋子, 山田清文, 鍋島俊隆

    第24回日本生物学的精神医学会 

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    Event date: 2002.4

    Language:Japanese  

    Country:Japan  

  167. Neuronal mechanism for the expression of methamphetamine (MAP)-indeuced conditioned place preference (CPP) in rats.

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    Event date: 2002.3

    Language:English  

  168. Changes in expression level of TNF-alpha and its receptor TNF-R1 mRNA in the brain of methamphetamine- and morphine-treated rats.

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    Event date: 2002.3

    Language:English  

    Country:Japan  

  169. オピオイド系鎮痛薬と神経刺激薬に共通した薬物依存の形成機構.科学技術振興調整費目標達成脳科学研究「依存性薬物により誘発される精神障害の機構の解明の研究」

    山田清文, 宮本嘉明, 水野誠, Jue He, 中島晶, 永井拓, 溝口博之, 内山武久, 吉村正子, 水野朋子, 石川和宏, 野田幸裕, 鍋島俊隆

    平成13年度班会議 

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    Event date: 2002.2

    Language:Japanese  

  170. メタンフェタミンの精神依存および神経毒性におけるTNF-αの役割.(シンポジウム48「薬物依存と精神障害」)

    山田清文, 中島晶, 溝口博之, 内山武久, 宮本嘉明, 石川和宏, 鍋島俊隆

    第44回日本神経化学会・第24回日本神経科学大会合同大会 

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    Event date: 2001.9

    Language:Japanese  

    Country:Japan  

  171. メタンフェタミンの条件性場所嗜好反応の発現に伴うmitogen-activated protein kinases (MAPK) の活性化

    山田清文, 水野誠, 溝口博之, 宮本嘉明, 鍋島俊隆

    第4回ニコチン・薬物依存研究フォーラム学術年会 

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    Event date: 2001.7

    Language:Japanese  

    Country:Japan  

  172. 覚せい剤依存症モデルラットの意思決定障害と島皮質 International conference

    溝口博之, 福本和哉, 山田清文

    日本薬学会 第135 年会  2015.3 

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:神戸  

  173. 島皮質は薬物依存症モデルラットの意思決定に関与する International conference

    溝口博之, 山田清文

    第88 回日本薬理学会 年会  2015.3 

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:名古屋  

  174. 島皮質GABA神経の機能操作は意思決定に影響する International conference

    溝口博之, 犬束 歩, 片平健太郎, 山田清文

    次世代を担う創薬・医療管理シンポジウム  2017.8 

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:京都市  

  175. 依存性薬物がもたらす認知・意思決定異常 International conference

    溝口博之, 山田清文

    第40回日本神経科学大会  2017.7 

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    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:千葉市  

  176. リスク下の意思決定における島皮質GABA神経の役割. International conference

    溝口博之, 犬束 歩, 片平健太郎, 山田清文

    日本アルコール・アディクション医学会学術総会  2017.9 

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:横浜  

  177. ナノボディおよびDARPinを利用したRFP-dependent Creの開発 International conference

    犬束 歩, 溝口博之, 金子涼輔, 尾仲達史

    第40回日本神経科学大会  2017.7 

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:千葉  

  178. タッチスクリーン式弁別課題を用いた認知機能解析システムの確立. International conference

    Md.Ali Bin Saifullah, 山中宏二, 溝口博之

    日本薬学会第138年会  2018.3 

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    Language:Japanese   Presentation type:Oral presentation (general)  

  179. タッチスクリーン式弁別課題を用いた認知機能解析システムの確立. International conference

    Md.Ali-Bin-Saifullah, 溝口博之

    次世代を担う創薬・医療管理シンポジウム  2017.8 

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    Language:Japanese   Presentation type:Poster presentation  

    Venue:京都  

  180. DREADD テクノロジーで報酬に基づく意思決定を操作する International conference

    中村旭宏, 溝口博之, 山田清文

    日本薬学会 第135年会  2015.3 

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    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:神戸  

▼display all

Works 2

  1. モノクロラミン誘起胃粘膜傷害に対するマレイン酸イルソグラジンの影響

    2000

  2. モノクロラミン誘起胃粘膜傷害に対するマレイン酸イルソグラジンの影響

    2000

Other research activities 1

  1. 薬剤師業務

Research Project for Joint Research, Competitive Funding, etc. 4

  1. 行動の固執性から探る依存症の解明

    2021.1 - 2022.3

    堀科学芸術振興財団 研究費助成事業 

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    Authorship:Principal investigator  Grant type:Competitive

  2. 報酬獲得行動におけるオレキシン神経とニコチン受容体の役割

    2020.4 - 2023.3

    公益財団法人 喫煙科学研究財団 

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    Grant type:Competitive

  3. 依存症抑止に向けたリスク志向な脳の解明

    2019.4 - 2021.3

    公益財団法人 武田科学振興財団 

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    Authorship:Principal investigator  Grant type:Competitive

  4. 食の価値・評価と行動選択の神経基盤の解明

    2019.4 - 2020.3

    公益財団法人 三島海雲記念財団 

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    Authorship:Principal investigator  Grant type:Competitive

KAKENHI (Grants-in-Aid for Scientific Research) 13

  1. Genomic analysis-based neuropharmacological study on basal ganglia-thalamocortical circuits for new drug discovery in schizophrenia

    Grant number:20H03428  2020.4 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Coinvestigator(s) 

  2. モデルベース行動選択試験によるギャンブル障害モデル動物の情報処理システムの解明

    Grant number:19K21811  2019.6 - 2022.3

    科学研究費助成事業  挑戦的研究(萌芽)

    溝口 博之

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    Authorship:Principal investigator 

    Grant amount:\6500000 ( Direct Cost: \5000000 、 Indirect Cost:\1500000 )

    意思決定に必要な習慣的システムと目的指向的システムは連続的、並列的な関係で、どちらかの能力が劣っているわけでもない。げっ歯類の脳内でのシステム間連係を計算論的に表現できれば、高次脳機能の理解に繋がるものの、基礎研究において、システム間バランスに注目した意思決定研究は少ない。また、システム間バランス異常に関与する責任脳領域は不明であり、それを打破する策として、精神疾患モデル動物を用いることで、明らかになると考える。本研究では、ギャンブル障害モデル動物を用いて、意思決定システム間バランスを評価する行動試験の開発・発展と情報処理システムの解明に挑戦する。
    意思決定を行うには、習慣的システムと目的指向的システムが状況に応じて切り替わりながら、協調的に働くことが必要である。これら情報処理システムの協調的バランスに問題が生じると、自己制御能力の低下や近視眼的意思決定に繋がる。意思決定に異常があると言われている精神疾患に依存症がある。依存症の中で社会的且つ医薬学的対策が急務なのはギャンブル障害であるが、ギャンブル障害において情報処理システム間のバランス破綻に着目した報告は少ない。本研究では、意思決定システム間バランスを評価する行動試験の開発・発展と情報処理システムの解明に挑戦する。本年度は、統計解析ソフトR および確率的プログラミング言語stanを用いて強化学習モデルに基づくパラメータ推定を行うプログラムの作成を行った。Stanにデータを渡すために、実験データの前処理を行い、Stanによるパラメータ推定の結果を表、グラフなどによって視覚化するプログラムを作成した。タスクには第1段階、第2段階があり、臨床研究を参考に、SARSA(λ)時間差(TD)アルゴリズムを使用して、モデル化した。Stanのパラメータ推定のプログラムをRに書き換え、改変して、データを作り出すシミュレーションのプログラムを作成中である。Stanではデバッグしにくいが、Rでは途中段階のデータ状況が確認できるため、計算の動作確認とプログラムの問題点の洗い出しの目的で進めている。今後は実際の動物データを入れ込みパラメータ推定を行う予定である。また、間接路の特異的な遺伝子をノックダウン、特にDRD2をノックダウンさせるため、CRISPR/Cas9システムを導入し、in vitro実験を行ったが、特異的なノックダウン効果が確認できなかった。今後は、ノックダウンシステムの再構成とin vivo実験における効果確認を行う予定でいる。
    計算論のパラメータ推定に向けたプログラムの構築は進んでいるものの、行動実験に少し遅れが出ている。
    今年度は、引き続きモデルフィット化に向けたプログラムの作成を行うとともに、実際の動物データを入れ込みパラメータ推定を行う予定である。また、間接路の特異的な遺伝子をノックダウンシステムの確立させるため、ノックダウンシステムの再構成とin vivo実験における効果確認を行う予定でいる。

  3. リスク志向な意思決定の神経基盤:行動・神経回路操作・計算論的手法によるアプローチ

    Grant number:19H03532  2019.4 - 2022.3

    科学研究費助成事業  基盤研究(B)

    溝口 博之, 犬束 歩, 片平 健太郎

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    Authorship:Principal investigator 

    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

    依存症は健康を脅かす疾患であり、ギャンブル障害、ゲーム障害などが新たに精神疾患として認定されるなど、今まで以上に身近な社会問題として懸念されている。この事から新たな依存症の包括的理解に向けた機序解明が必要である。本研究では、多種多様な遺伝子発現制御法と遺伝子改変ラットを用いて、島皮質を基軸とした意思決定・行動選択の変容に関わる領域間ネットワーク、神経-神経ネットワークを解明し、依存症の新たな治療戦略の発信を目指す。
    本研究では、多種多様な遺伝子発現制御法と遺伝子改変ラットを用いて、島皮質を基軸とした意思決定・行動選択の変容に関わる領域間ネットワーク、神経-神経ネットワークを解明する。ラットの意思決定の解析は、ラット用ギャンブル試験を使用する(PNAS, 2015; Behav Brain Res, 2019)。この解析手法を用いると正
    常動物は、リスク回避行動を示すことが分かっている。昨年度は、DRD2-Creラットを用いて間接路の神経脱落がリスク回避行動を促す可能性について例数を追加し、結論を得た。さらに、新規逆行性rAAV-Flp(FLP/FRTシステム)を用いると経路特異的に遺伝子を発現させることができることを免疫組織学的検討により確認した。また、DRD2-CreラットとRosa-tdTomatoラットとを交配させ、間接路特異的にtdTomatoが発現するラットを作製した。このラットを用いて、島皮質から入力する信号が間接路にどのような影響を及ぼすか、電気生理学的セットアップを行った。今年度はホールセルパッチクランプ法を用いて電気生理学的に島皮質からの線条体への入力の役割を検討した。島皮質-線条体回路にチャネルロドプシンを発現させ、線条体・側坐核の直接路、間接路への入力について検討した。しかし、思った以上に発現細胞の数の少なさから目的としていた結果は得られなかった。用いた手技には相当な発現細胞の数が必要であることが分かった。現在はc-Fos染色に切り替えて検討を行う事にした。また、昨年度間接路特異的な遺伝子発現をコントロールするため、新たにCRISPR/Cas9システムの導入に向けたプロジェクトを発足させ、in vitroレベルでの構築を始めた。今年度は作製したウイルスの効果を培養細胞系で検討したが、明確な反応は見られなかった。そこで、in vivoで検討することにし、現在行っている。
    ホールセルパッチクランプ法を用いて電気生理学的に島皮質からの線条体への入力の役割を検討したが、発現細胞の数の少なさから目的としていた結果は得られなかった。用いた手技には相当な発現細胞の数が必要であることが分かったので、現在はc-Fos染色に切り替えて検討を行う事にした。
    島皮質-線条体回路特異的にDREADD(M3Dq)を発現させ、CNOを投与した時のc-Fos発現から線条体への入力が直接路、間接路のどの脳領域に入力しているかを検討する。最終年度であることから現在得られたデータを中心に論文化を目指す。

  4. 不確実な状況下における報酬動機づけメカニズムとオレキシン神経活動

    Grant number:19H05017  2019.4 - 2021.3

    科学研究費助成事業  新学術領域研究(研究領域提案型)

    溝口 博之

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    Authorship:Principal investigator 

    Grant amount:\7800000 ( Direct Cost: \6000000 、 Indirect Cost:\1800000 )

    「意志力」は自己をコントロールし、難局を打開するのに必要な力である。意志力を強化することは、ストレス社会を生き抜く術である。我々は以前に、オレキシン神経の活性化は諦めない行動(意志力)に関わることを見つけ、自己コントロールにおけるオレキシン神経系の機能的役割を行動学的に明らかにした。しかし、①意志力検証実験中オレキシン神経は活性化しているのか、②課題遂行中のどのタイミングのオレキシン神経活動が、課題成功率にかかわるのかは不明である。そこで本研究では光遺伝学的手法を導入し、オレキシン神経活動の測定と、操作した時の報酬動機づけ行動への影響を検討する。
    「意志力」は自己をコントロールし、難局を打開するのに必要な力である。我々は、オレキシン神経の活性化は報酬獲得に対するモチベーションの増加(諦めな
    い行動)や確率逆転学習の成功率の低下に関わることを見つけ、自己コントロールにおけるオレキシン神経系の機能的役割を行動学的に実証した。しかし、①意
    志力検証実験中オレキシン神経は活性化しているのか、②課題遂行中のどのタイミングのオレキシン神経活動が、課題成功率にかかわるのかは不明である。本研
    究では、光遺伝学的手法を導入し、オレキシン神経活動の測定と、操作した時の意志力行動への影響を検討した。タッチスクリーン式弁別試験を用いて、意志力
    による自己コントロールにおけるオレキシン神経の機能的役割について検討した。昨年度は、progressive ratio試験においてオレキシン神経を脱落させると、有
    意なやる気行動の低下が認められたが、メチルフェニデートを投与すると、緩解する傾向があることが分かった。今年度は無線式ファイバーフォトメトリーを導入して、報酬獲得行動におけるオレキシン神経活動を測定した。Orexin-Creラットの視床下部にAAV-FLEX-GCaMPを感染させ、オレキシン神経特異的にカルシウムセンサーを発現させ、蛍光強度を測定することで、神経活動の指標とした。その結果、オレキシン神経活動は報酬獲得行動時に増加することを見つけた。さらにその増加は餌を食べることで低下する可能性も見つけた。このことから、オレキシン神経は摂食行動というよりかは食欲行動に関係する可能性が示唆された。今後は例数を追加していきたいと考えている。
    令和2年度が最終年度であるため、記入しない。
    令和2年度が最終年度であるため、記入しない。

  5. オレキシン神経特異的機能操作による動機づけ神経回路の解明と意志力検証技術の開発

    Grant number:17H06053  2017.4 - 2019.3

    新学術領域研究(研究領域提案型)

    溝口 博之

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    Authorship:Principal investigator 

    Grant amount:\8840000 ( Direct Cost: \6800000 、 Indirect Cost:\2040000 )

    報酬に対する動機づけとしてギャンブル試験を、課題に対する動機づけとしてタッチスクリーン式弁別試験を用いることで、意志力を検証できるシステムを構築した。また、orexin BAC-Creラットを用いて、オレキシン神経特異的にDesigner Receptors Exclusively Activated by Designer Drugs (DREADD)を発現させ、動機づけ行動におけるオレキシン神経の役割を明らかにしてきた。
    特に平成30年度は、オレキシン神経の活性化は諦めない行動や確率逆転学習にも影響することを見つけ、課題に対する動機づけ行動に影響を及ぼすことが分かった。また、ギャンブル試験の行動データを計算論モデリングしたところ、オレキシン神経を活性化させるとハイリターンに対する期待値が高くなることが分かった。これらの事から、オレキシン神経はやる気・意志力に関わる神経回路の一旦を担う可能性が示され、特に、オレキシン神経は不確実な状況下における報酬に対する期待値に影響を及ぼす可能性があることが分かった。また、オレキシン神経の活性化は摂食量、摂水量を増加させることが分かった。しかし、行動量については影響なかった。これらの結果から、オレキシン神経の活性化は既報と同じように本能行動に影響することが示された。また、現在検討中であるが、蛍光イメージングシステム(ファイバーフォトメトリー)を用いて、動機づけにおけるオレキシン神経活動を測定し、オレキシン神経を光操作したときの動機づけ行動について検討している。このイメージング実験についてはシステムの工夫が必要であると考えている。
    平成30年度が最終年度であるため、記入しない。
    平成30年度が最終年度であるため、記入しない。

  6. Research on neural circuit in decision-making by using cell- and projection-specific manner of chemogenetics and computational approach

    Grant number:16H03303  2016.4 - 2019.3

    Mizoguchi Hiroyuki

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    Authorship:Principal investigator 

    Grant amount:\17160000 ( Direct Cost: \13200000 、 Indirect Cost:\3960000 )

    Decision-making is a key activity process that influences many aspects of daily living and both mental and physical health. In general, healthy participants reveal rational choice, but patients with neuropsychiatric disorders reveal irrational and risky choice in decision-making. A better understanding of the mechanisms underlying altered decision-making would provide insights into potential therapeutic approaches for these diseases. However, the neural pathway and substrates underlying these deficits are particularly unknown. In this research, we demonstrated that insular cortex, nucleus accumbens, and striatum are key regions for risky decision-making. Our findings suggest that disinhibition of glutamatergic neurons as well as dysfunction of GABAergic interneurons in the insular cortex, plays a role in altered decision-making. Further research on the insular-striatal pathway would be necessary to understand the mechanisms underlying impaired decision-making.

  7. A novel behavioral task for investigating a mixture of model-free and model-based reinforcement learning in rodents

    Grant number:16K13505  2016.4 - 2018.3

    Mizoguchi Hiroyuki

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    Authorship:Principal investigator 

    Grant amount:\3380000 ( Direct Cost: \2600000 、 Indirect Cost:\780000 )

    Decision-making and reinforcement learning arise from the involvement of two distinct processes that control choice, known as model-based and model-free strategies. Model-based choices are prospective, whereas model-free choices are retrospective. In general, normal performance depends on the flexible integration of model-based and model-free control. In this research, we employed a two-step sequential visual discrimination learning of complex stimuli in touch-screen task to establish a novel behavioral system for investigating a mixture of model-free and model-based reinforcement learning in rodent. Rats chose option on the reward amount- and provability-dependent manner. However, we failed to find best fitting behavioral modeling and parameters. We need to continue our experiments in future studies.

  8. Study on the neuronal circuit and molecular mechanis underlying decision-making and its application for drug development

    Grant number:26293053  2014.4 - 2017.3

    Yamada Kiyofumi

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    Authorship:Coinvestigator(s) 

    Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders have impairments in decision-making, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-dependent rats choose a high-risk/high-reward option more frequently, and assign higher subjective value to high returns, than control rats, suggesting that decision-making is impaired in the drug-dependent animals. Immunohistochemical analysis following the gambling test revealed aberrant activation of the insular cortex (INS) and nucleus accumbens in METH-dependent animals. Pharmacological studies together with in vivo microdialysis showed that GABAergic neurotransmission in INS played a crucial role in decision-making. Moreover, manipulation of INS activation using DREADD technology resulted in alterations to decision-making.

  9. DREADDシステムと計算論的手法を用いた近視眼的意思決定の追究

    Grant number:26120713  2014.4 - 2016.3

    新学術領域研究(研究領域提案型)

    溝口 博之

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    Authorship:Principal investigator 

    Grant amount:\10530000 ( Direct Cost: \8100000 、 Indirect Cost:\2430000 )

    精神病患者にみられる意思決定(実行機能など)の障害は生体ホメオスタシスの制御機構の変化 (Science, 2007)、近い将来の快感に関連する扁桃体を含む衝動的神経回路と遠い将来に関係する思慮的な前頭葉皮質回路のアンバランス (Nat Neurosci, 2005) に基づくと提唱されているが、意思決定障害の研究は他の精神異常と比べて明らかに遅れている。それゆえ、この分野の小動物を用いた研究の発展は、意思決定異常時における脳内プロセスの解明に大きな研究成果を残し、さらには、精神疾患患者を対象とした臨床応用研究・治療などの方向性を明確に定めると期待できる。昨年度は、島皮質をDREADDテクノロジーで操作することで、意思決定・行動選択を操作出来ることを確認し、さらには、覚せい剤誘発意思決定障害について、計算論的手法を用いて、モデル化することができた。今年度は、意思決定における大脳基底核の直接路、間接路の役割について検討した。その結果、直接路をDREADDテクノロジーで活性化させると、リスク志向な意思決定を示すことが分かった。また、計算論的手法を用いて、その行動選択をモデル化したところ、その行動は探索的である可能性が示されたが、この点については詳細な検討が必要である。一方、間接路を活性化させても行動選択に影響はなかった。この点についても遺伝子の発現量やウイルスベクターの選択性による影響が大きいことから、詳細な検討が必要と考えている。
    27年度が最終年度であるため、記入しない。
    27年度が最終年度であるため、記入しない。

  10. Effect of nicotine on reward-based decision-making in healthy and methamphetamine-treated rat

    Grant number:25460094  2013.4 - 2016.3

    Mizoguchi Hiroyuki

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    Authorship:Principal investigator 

    Grant amount:\5070000 ( Direct Cost: \3900000 、 Indirect Cost:\1170000 )

    In this study, we examined the effects of nicotine on reward-based decision-making in healthy and methamphetamine (METH)-treated rat. We analyzed the performance of rats in a gambling test for rodents. Nicotine treatment (0.3 mg/kg) ameliorated the abnormal arm-choice behavior of METH-treated rats in the gambling test. However, chronic nicotine treatment (0.3 or 0.6 mg/kg) did not show changes in arm-choice behavior in healthy rats. Our findings suggest that nicotine may have some therapeutic effects against impairment of decision-making in METH addicts.

  11. 依存性薬物による意思決定障害の行動解析と画像診断

    2011.5 - 2013.3

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

  12. てんかん発作感受性遺伝子MMPの機能的役割と発現機構の網羅的解析

    2009.4 - 2011.3

    科学研究費補助金  若手研究(B)

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    科学研究費補助金若手B, 課題番号21790068 H21-22年度 3,810,000

  13. 薬物依存の形成機序に解明―マトリクスメタロプロテアーゼの関与―

    2006.4 - 2008.3

    科学研究費補助金  若手研究(B)

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Teaching Experience (On-campus) 3

  1. 特徴あるプログラム「医薬統合プログラム」

    2020

  2. 臨床薬理学

    2020

  3. 自然環境と人間

    2020

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    脳科学と疾患の授業(2コマ)を行った。