研究者詳細 - 溝口　博之

論文 - 溝口　博之

分割表示 146 件中 41 - 60 件目／全件表示 >>

溝口博之, 王天, Saifullah Md. Ali Bin, 福本和哉, 山田清文

日本薬理学会年会要旨集 92 巻 ( 0 ) 頁： 1-P-023 - P-023 2019年

記述言語：日本語出版者・発行元：公益社団法人日本薬理学会

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.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.

DOI： 10.1254/jpssuppl.92.0_1-p-023

CiNii Research

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

Saifullah MD. Ali Bin, 小峯起, 祖父江顕, 山中宏二, 溝口博之

日本薬理学会年会要旨集 92 巻 ( 0 ) 頁： 1-P-041 - P-041 2019年

記述言語：日本語出版者・発行元：公益社団法人日本薬理学会

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 APPNL-G-F/NL-G-F knock-in (APP-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 APP-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 APP-KI mice at an early (4 months) stage while classical behavioral tests shows comparable results between wild-type and disease model mice.

DOI： 10.1254/jpssuppl.92.0_1-p-041

CiNii Research

認知症との共生社会を支える基礎研究 Open Access

柳井修一, 髙瀨堅吉, 山口哲生, 内田さえ, 泉尾直孝, 溝口博之, 稲垣宏樹, 日下菜穂子

日本心理学会大会発表論文集 82 巻 ( 0 ) 頁： SS-029 - SS-029 2018年9月

AN OPERANT TASK FOR TESTING RISKY DECISION-MAKING IN MICE

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

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH 42 巻頁： 48A - 48A 2018年8月

ギャンブル障害の現状と薬剤師の役割査読有り

溝口博之

医薬ジャーナル 54(4) 巻頁： 1037 - 1040 2018年

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 53 巻 ( 9 ) 頁： 923 - 923 2017年

記述言語：日本語出版者・発行元：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CHRNA5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． 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． 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. 1) Tobacco and Genetics Consortium., Nat. Genet., 42, 441–447(2010). 2) Schizophrenia Working Group of the Psychiatric Genomics Consortium., Nature, 511, 421–427(2014). 3) Proulx E. et al., Cell. Mol. Life Sci., 71, 1225-1244(2014). 4) Koukouli F. et al., Nat. Med., 23, 347–354(2017).

DOI： 10.14894/faruawpsj.53.9_923

CiNii Research

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 25 巻頁： 115 - 116 2016年9月

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, Y; Katanosaka, K; Mizoguchi, H; Murata, Y

NEUROBIOLOGY OF AGING 43 巻頁： 34 - 46 2016年7月

記述言語：英語出版者・発行元：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

Web of Science

Scopus

PubMed

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments. 査読有り Open Access

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 : JASN 27 巻 ( 3 ) 頁： 766 - 80 2016年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of the American Society of Nephrology

Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancermay also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3-CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggesting an underlying mechanism of impaired long-term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality.

DOI： 10.1681/ASN.2014121196

Scopus

PubMed

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

Mizoguchi, H; Yamanaka, A; Yamada, K

JOURNAL OF PHARMACOLOGICAL SCIENCES 130 巻 ( 3 ) 頁： S73 - S73 2016年3月

Insular neural system controls decision-making in healthy and methamphetamine-treated rats. 査読有り Open Access

Mizoguchi H, Katahira K, Inutsuka A, Fukumoto K, Nakamura A, Wang T, Nagai T, Sato J, Sawada M, Ohira H, Yamanaka A, Yamada K

Proceedings of the National Academy of Sciences of the United States of America 112 巻 ( 29 ) 頁： E3930 - 9 2015年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Proceedings of the National Academy of Sciences of the United States of America

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

Scopus

PubMed

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

Mizoguchi, H; Yamada, K

JOURNAL OF PHARMACOLOGICAL SCIENCES 128 巻 ( 3 ) 頁： S61 - S61 2015年7月

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 査読有り国際誌 Open Access

Hada, K; Wulaer, B; Nagai, T; Itoh, N; Sawahata, M; Sobue, A; Mizoguchi, H; Mori, D; Kushima, I; Nabeshima, T; Ozaki, N; Yamada, K

MOLECULAR BRAIN 14 巻 ( 1 ) 頁： 21 - 21 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Molecular Brain

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

Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer's disease 査読有り国際誌 Open Access

Sobue, A; Komine, O; Hara, Y; Endo, F; Mizoguchi, H; Watanabe, S; Murayama, S; Saito, T; Saido, TC; Sahara, N; Higuchi, M; Ogi, T; Yamanaka, K

ACTA NEUROPATHOLOGICA COMMUNICATIONS 9 巻 ( 1 ) 頁： 1 - 1 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Acta Neuropathologica Communications

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.

DOI： 10.1186/s40478-020-01099-x

Analysis of Reelin signaling and neurodevelopmental trajectory in primary cultured cortical neurons with RELN deletion identified in schizophrenia. 招待有り査読有り

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. 144 巻頁： 104954 2021年1月

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 査読有り Open Access

Saifullah, MAB; Komine, O; Dong, YT; Fukumoto, K; Sobue, A; Endo, F; Saito, T; Saido, TC; Yamanaka, K; Mizoguchi, H

MOLECULAR BRAIN 13 巻 ( 1 ) 頁： 147 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Molecular Brain

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.

DOI： 10.1186/s13041-020-00690-6

Methamphetamine use causes cognitive impairment and altered decision-making 査読有り

Mizoguchi, H; Yamada, K

NEUROCHEMISTRY INTERNATIONAL 124 巻頁： 106 - 113 2019年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Neurochemistry International

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.

DOI： 10.1016/j.neuint.2018.12.019

Web of Science

Scopus

PubMed

AN OPERANT TASK FOR TESTING RISKY DECISION-MAKING IN MICE

Wang T, Fukumoto K, Mizoguchi H, Yamada K

ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH 42 巻頁： 48A-48A 2018年8月

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 381 巻頁： 714-715 - 715 2017年10月

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

Takagishi Y, Katanosaka K, Mizoguchi H, Murata Y

Neurobiology of Aging 43 巻頁： 34-46 2016年7月

　前のページ - 次のページ　

<溝口 博之>

論文 - 溝口 博之

<溝口　博之>

論文 - 溝口　博之