Updated on 2022/05/13

写真a

 
NAKAMURA Yoshiko
 
Organization
Graduate School of Medicine Program in Integrated Medicine Cell Science Lecturer
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Lecturer

Degree 1

  1. 博士(医学) ( 京都大学 ) 

Research Interests 4

  1. 摂食代謝調節

  2. プロスタグランジン

  3. 発熱

  4. 体温調節

Current Research Project and SDGs 1

  1. 体温調節の神経メカニズム

Awards 5

  1. 自律神経学会学会賞

    2018   日本自律神経学会  

    中村佳子

  2. The Professor Geoffrey Burnstock Awards for Young Investigators

    2017   ISAN  

    Yoshiko Nakamura

  3. FASEB Summer Research Conferences “Neural Mechanisns in Cardiovascular Regulation" 2013 Travel Award

    2013  

    Yoshiko Nakamura

  4. Young Researcher Award

    2009   国際温熱学会  

    中村佳子

  5. Young Scientists Award

    2006.3   国際温熱学会  

    中村佳子

 

Papers 11

  1. A hypothalamomedullary network for physiological responses to environmental stresses. Reviewed

    Nakamura, K.*, Nakamura, Y. & Kataoka, N.

    Nature Rev. Neurosci.   Vol. 23 ( 1 ) page: 35 - 52   2022.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41583-021-00532-x.

  2. Hunger and Satiety Signaling: Modeling Two Hypothalamomedullary Pathways for Energy Homeostasis Invited Reviewed

    Nakamura Kazuhiro, Nakamura Yoshiko

    BIOESSAYS   Vol. 40 ( 8 )   2018.8

  3. Central regulation of brown adipose tissue thermogenesis and energy homeostasis dependent on food availability Invited Reviewed

    Nakamura Yoshiko, Nakamura Kazuhiro

    PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY   Vol. 470 ( 5 ) page: 823 - 837   2018.5

  4. The lateral parabrachial nucleus, but not the thalamus, mediates thermosensory pathways for behavioural thermoregulation Reviewed

    Yahiro Takaki, Kataoka Naoya, Nakamura Yoshiko, Nakamura Kazuhiro

    SCIENTIFIC REPORTS   Vol. 7   2017.7

  5. Medullary Reticular Neurons Mediate Neuropeptide Y-Induced Metabolic Inhibition and Mastication Reviewed

    Nakamura Yoshiko, Yanagawa Yuchio, Morrison Shaun F., Nakamura Kazuhiro

    CELL METABOLISM   Vol. 25 ( 2 ) page: 322 - 334   2017.2

  6. DISTRIBUTION OF FOS-IMMUNOREACTIVE CELLS IN RAT FOREBRAIN AND MIDBRAIN FOLLOWING SOCIAL DEFEAT STRESS AND DIAZEPAM TREATMENT Reviewed

    B. Lkhagvasuren, T. Oka, Y. Nakamura, H. Hayashi, N. Sudo, K. Nakamura

    NEUROSCIENCE   Vol. 272   page: 34 - 57   2014.7

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:PERGAMON-ELSEVIER SCIENCE LTD  

    The anxiolytic diazepam selectively inhibits psychological stress-induced autonomic and behavioral responses without causing noticeable suppression of other central performances. This pharmacological property of diazepam led us to the idea that neurons that exhibit diazepam-sensitive, psychological stress-induced activation are potentially those recruited for stress responses. To obtain neuroanatomical clues for the central stress circuitries, we examined the effects of diazepam on psychological stress-induced neuronal activation in broad brain regions. Rats were exposed to a social defeat stress, which caused an abrupt increase in body temperature by up to 2 C. Pretreatment with diazepam (4 mg/kg, i.p.) attenuated the stress-induced hyperthermia, confirming an inhibitory physiological effect of diazepam on the autonomic stress response. Subsequently, the distribution of cells expressing Fos, a marker of neuronal activation, was examined in 113 forebrain and midbrain regions of these rats after the stress exposure and diazepam treatment. The stress following vehicle treatment markedly increased Fos-immunoreactive (IR) cells in most regions of the cerebral cortex, limbic system, thalamus, hypothalamus and midbrain, which included parts of the autonomic, neuroendocrine, emotional and arousal systems. The diazepam treatment significantly reduced the stress-induced Fos expression in many brain regions including the prefrontal, sensory and motor cortices, septum, medial amygdaloid nucleus, medial and lateral preoptic areas, parvicellular paraventricular hypothalamic nucleus, dorsomedial hypothalamus, perifornical nucleus, tuberomammillary nucleus, association, midline and intralaminar thalami, and median and dorsal raphe nuclei. In contrast, diazepam increased Fos-IR cells in the central amygdaloid nucleus, medial habenular nucleus, ventromedial hypothalamic nucleus and magnocellular lateral hypothalamus. These results provide important information for elucidating the neural circuitries that mediate the autonomic and behavioral responses to psychosocial stressors. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.neuroscience.2014.04.047

    Web of Science

  7. EP<sub>3</sub> receptors mediate PGE<sub>2</sub>-induced hypothalamic paraventricular nucleus excitation and sympathetic activation Reviewed

    Z.-H. Zhang, Y. Yu, S.-G. Wei, Y. Nakamura, K. Nakamura, R.B. Felder

    American Journal of Physiology - Heart and Circulatory Physiology   Vol. 301 ( 4 ) page: H1559-H1569   2011

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1152/ajpheart.00262.2011

  8. Social defeat stress induces hyperthermia through activation of thermoregulatory sympathetic premotor neurons in the medullary raphe region Reviewed

    B. Lkhagvasuren, Y. Nakamura, T. Oka, N. Sudo, K. Nakamura

    European Journal of Neuroscience   Vol. 34 ( 9 ) page: 1442 - 1452   2011

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/j.1460-9568.2011.07863.x

  9. DIFFERENT POPULATIONS OF PROSTAGLANDIN EP3 RECEPTOR-EXPRESSING PREOPTIC NEURONS PROJECT TO TWO FEVER-MEDIATING SYMPATHOEXCITATORY BRAIN REGIONS Reviewed

    Y. Nakamura, K. Nakamura, S. F. Morrison

    NEUROSCIENCE   Vol. 161 ( 2 ) page: 614 - 620   2009.6

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    Publishing type:Research paper (scientific journal)   Publisher:PERGAMON-ELSEVIER SCIENCE LTD  

    The central mechanism of fever induction is triggered by an action of prostaglandin E(2) (PGE(2)) on neurons in the preoptic area (POA) through the EP3 subtype of prostaglandin E receptor. EP3 receptor (EP3R)-expressing POA neurons project directly to the dorsomedial hypothalamus (DMH) and to the rostral raphe pallidus nucleus (rRPa), key sites for the control of thermoregulatory effectors. Based on physiological findings, we hypothesize that the febrile responses in brown adipose tissue (BAT) and those in cutaneous vasoconstrictors are controlled independently by separate neuronal pathways: PGE2 pyrogenic signaling is transmitted from EP3R-expressing POA neurons via a projection to the DMH to activate BAT thermogenesis and via another projection to the rRPa to increase cutaneous vasoconstriction. In this case, DMH-projecting and rRPa-projecting neurons would constitute segregated populations within the EP3R-expressing neuronal group in the POA. Here, we sought direct anatomical evidence to test this hypothesis with a double-tracing experiment in which two types of the retrograde tracer, cholera toxin b-subunit (CTb), conjugated with different fluorophores were injected into the DMH and the rRPa of rats and the resulting retrogradely labeled populations of EP3R-immunoreactive neurons in the POA were identified with confocal microscopy. We found substantial numbers of EP3R-immunoreactive neurons in both the DMH-projecting and the rRPa-projecting populations. However, very few EP3R-immunoreactive POA neurons were labeled with both the CTb from the DMH and that from the rRPa, although a substantial number of neurons that were not immunoreactive for EP3R were double-labeled with both CTbs. The paucity of the EP3R-expressing neurons that send collaterals to both the DMH and the rRPa suggests that pyrogenic signals are sent independently to these caudal brain regions from the POA and that such pyrogenic outputs from the POA reflect different control mechanisms for BAT thermogenesis and for cutaneous vasoconstriction by distinct sets of POA neurons. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.neuroscience.2009.03.041

    Web of Science

  10. Direct pyrogenic input from prostaglandin EP3 receptor-expressing preoptic neurons to the dorsomedial hypothalamus Reviewed

    Nakamura Y, Nakamura K, Matsumura K, Kobayashi S, Kaneko T, Morrison SF

    FASEB JOURNAL   Vol. 20 ( 4 ) page: A366 - A366   2006.3

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    Publishing type:Research paper (scientific journal)  

    Web of Science

  11. Identification of sympathetic premotor neurons in medullary raphe regions mediating fever and other thermoregulatory functions Reviewed

    K Nakamura, K Matsumura, T Hubschle, Y Nakamura, H Hioki, F Fujiyama, Z Boldogkoi, M Konig, HJ Thiel, R Gerstberger, S Kobayashi, T Kaneko

    JOURNAL OF NEUROSCIENCE   Vol. 24 ( 23 ) page: 5370 - 5380   2004.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SOC NEUROSCIENCE  

    Sympathetic premotor neurons directly control sympathetic preganglionic neurons (SPNs) in the intermediolateral cell column (IML) of the thoracic spinal cord, and many of these premotor neurons are localized in the medulla oblongata. The rostral ventrolateral medulla contains premotor neurons controlling the cardiovascular conditions, whereas rostral medullary raphe regions are a candidate source of sympathetic premotor neurons for thermoregulatory functions. Here, we show that these medullary raphe regions contain putative glutamatergic neurons and that these neurons directly control thermoregulatory SPNs. Neurons expressing vesicular glutamate transporter 3 (VGLUT3) were distributed in the rat medullary raphe regions, including the raphe magnus and rostral raphe pallidus nuclei, and mostly lacked serotonin immunoreactivity. These VGLUT3-positive neurons expressed Fos in response to cold exposure or to central administration of prostaglandin E-2, a pyrogenic mediator. Transneuronal retrograde labeling after inoculation of pseudorabies virus into the interscapular brown adipose tissue (BAT) or the tail indicated that those VGLUT3-expressing medullary raphe neurons innervated these thermoregulatory effector organs multisynaptically through SPNs of specific thoracic segments, and microinjection of glutamate into the IML of the BAT-controlling segments produced BAT thermogenesis. An anterograde tracing study further showed a direct projection of those VGLUT3-expressing medullary raphe neurons to the dendrites of SPNs. Furthermore, intra-IML application of glutamate receptor antagonists blocked BAT thermogenesis triggered by disinhibition of the medullary raphe regions. The present results suggest that VGLUT3-expressing neurons in the medullary raphe regions constitute excitatory neurons that could be categorized as a novel group of sympathetic premotor neurons for thermoregulatory functions, including fever.

    DOI: 10.1523/JNEUROSCI.1219-04.2004

    Web of Science

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MISC 5

  1. 飢餓から生命を守るための脳の仕組み Invited

    中村和弘, 中村佳子

    脳神経内科   Vol. 90 ( 6 ) page: 618 - 626   2019.6

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

  2. 飢餓反応の中枢神経回路メカニズム Invited

    中村 和弘, 中村 佳子

    肥満研究   Vol. 23 ( 2 ) page: 161 - 168   2017.9

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  3. Social defeat stress activates thermoregulatory sympathetic premotor neurons in the rostral medullary raphe

    Kazuhiro Nakamura, Lkhagvasuren Battuvshin, Yoshiko Nakamura, Takakazu Oka

    FASEB JOURNAL   Vol. 25   2011.4

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  4. Sympathetic premotor neurons mediating febrile responses and thermoregulatory functions

    K Nakamura, K Matsumura, T Hubschle, SX Wu, Y Nakamura, R Gerstberger, S Kobayashi, T Kaneko

    FASEB JOURNAL   Vol. 19 ( 5 ) page: A1191 - A1191   2005.3

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  5. Identification of sympathetic premotor neurons mediating fever and thermoregulation in the rostral ventromedial medulla

    Nakamura Kazuhiro, Kobayashi Shigeo, Kaneko Takeshi, Matsumura Kiyoshi, Huebschle Thomas, Nakamura Yoshiko, Wu Sheng-Xi, Okamoto Keiko, Fujiyama Fumino, Hioki Hiroyuki, Gerstberger Ruediger

    Proceedings of Annual Meeting of the Physiological Society of Japan   Vol. 2004 ( 0 ) page: S196 - S196   2004

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:PHYSIOLOGICAL SOCIETY OF JAPAN  

    The rostral ventromedial medulla (RVMM) sympathetically regulates thermogenesis in brown adipose tissue (BAT) and constriction of skin blood vessels. However, the sympathetic-related neurons in the RVMM remain to be identified. First, we found that vesicular glutamate transporter 3 (VGLUT3) -immunoreactive neurons in the rostral raphe pallidus nucleus and raphe magnus nucleus expressed Fos in response to both fever-inducing stimulus (central injection of prostaglandin E&lt;SUB&gt;2&lt;/SUB&gt;) and cold-exposure (4&amp;deg;C, 4 hours) in rats. Most of the VGLUT3-expressing neurons were negative for serotonin immunoreactivity, and many of them were labeled trans-synaptically with pseudorabies virus inoculated into rat interscapular BAT or tail. Furthermore, we found that the VGLUT3-positive neurons directly project onto sympathetic preganglionic neurons in the intermediolateral cell column (IML) of the spinal cord; and that VGLUT3-positive axon terminals in the IML formed asymmetric synapses, suggesting the excitatory characteristics of the synapses. These results suggest that the rostral medullary raphe regions contain glutamatergic neurons that could be categorized as a novel group of sympathetic premotor neurons involved in fever induction and thermoregulation. &lt;b&gt;[Jpn J Physiol 54 Suppl:S196 (2004)]&lt;/b&gt;

Presentations 9

  1. 飢餓反応の中枢神経回路メカニズム Invited

    蛋白研セミナー:食行動の脳内基盤と分子機構  2021 

  2. Medullary reticular GABAergic neurons that mediate hunger responses induced by hypothalamic neuropeptide Y Invited International conference

    2017 

  3. ニューロペプチドYによる代謝抑制を担う神経回路:飢餓を生き延びるための仕組み Invited

    第93回日本生理学会大会  2016.3 

  4. 体温調節と発熱の視索前野メカニズム Invited

    第35回日本神経科学大会  2012.8 

  5. The ways up and the ways down: dissecting neural pathways for thermoregulation Invited International conference

    6th Congress of the International Society for Autonomic Neuroscience (ISAN 2009)  2009 

  6. Differential control of thermal effector pathways contributing to fever Invited International conference

    36th International Congress of Physiological Sciences (IUPS2009) / 86th Annual Meeting of the Physiological Society of Japan  2009 

  7. Sympathetic premotor neurons mediating febrile responses and thermoregulatory functions Invited International conference

    The 35th Congress of the International Union of Physiological Sciences / Experimental Biology   2005 

  8. 温度知覚と体温調節行動は異なる温度感覚伝達路で駆動される Invited

    第95回日本生理学会大会  2018.3 

  9. ニューロペプチドYによる熱産生抑制と摂食亢進の神経メカニズム Invited

    生命科学系学会合同年次大会(ConBio2017)  2017.12 

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Research Project for Joint Research, Competitive Funding, etc. 2

  1. 恒常性維持を担う中枢神経回路の司令塔メカニズムの解明

    2017.4 - 2018.3

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\1000000

  2. 遺伝子改変ラットを用いた発熱スイッチニューロンの多面的機能解析

    2010

    京都大学  京都大学若手研究者スタートアップ研究費 

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    Authorship:Principal investigator 

    Grant amount:\850000

KAKENHI (Grants-in-Aid for Scientific Research) 4

  1. 体温調節中枢の局所回路と司令塔メカニズムの解明

    Grant number:21K06767  2021.4 - 2025.3

    基盤研究 (C)

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    Authorship:Principal investigator 

  2. 感染による食欲不振の中枢神経メカニズム

    Grant number:17K08568  2017.4 - 2021.3

    中村 佳子

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    Authorship:Principal investigator 

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    感染が起こると摂食の減少がみられることがあるがその神経メカニズムは分かっていない。本研究では、血液脳関門が比較的薄い脳室周囲器官に近く、血流からの様々な液性シグナル分子を受け取ると考えられる視索前野に着目し、感染症状発現の基盤をなす局所神経回路メカニズムの解明を進めている。視索前野には、発熱を惹起するメディエーターであるプロスタグランジンE2の受容体、EP3受容体を発現する神経細胞群(EP3ニューロン群)が存在しており、感染に伴って起こる摂食減少などの症状に関与する可能性が推測された。しかしながら、視索前野のEP3ニューロン群の特性は単一ではなく、多様な特性を持ったニューロンの集合で、予想以上に解明すべき点が多いことが本研究を継続している間にわかってきた。そのため、ラットに温度刺激をはじめとする様々な刺激を与え、視索前野のEP3ニューロン群の反応性や組織学的特性などを解析し、分類を継続して行なっている。EP3ニューロン群の細胞体を対象にした解析は、パッチクランプ法のような電気生理学的方法をはじめ、組織学的方法も駆使して解析を行っている。しかしながら、EP3ニューロン群の生理作用がどのような神経出力を介して生み出されるのかを考える場合、細胞体の解析だけでは不十分であり、視索前野のEP3ニューロン群の投射先軸索終末の性質や投射先の二次ニューロンとの関係を検討する必要がある。この点を踏まえ、視索前野のEP3ニューロン群の投射先を同定し、現在は投射先の神経終末も合わせて、その特性を詳細に解析している。また、神経活動操作法を用いてEP3ニューロン群を刺激あるいは抑制し、様々な環境刺激に対する応答性の変化も合わせて継時的に解析を行っている。
    昨年度に引き続き、視索前野のEP3ニューロン群の性質を知るために、ラットを暑熱暴露や寒冷刺激を行ってニューロンの活動をc-fosの発現を指標に組織学的に評価した。また、その細胞がどのような性質を持っているのかをin situ hybridization法や抗体を使った免疫組織学的手法を組み合わせて解析を行っている。また、ニューロンの投射先を同定し、どのような性質を持つ神経終末が投射し、下流の細胞をコントロールしているのかを詳細に解析している。神経活動操作法によって特定のニューロンを刺激、あるいは抑制することが、温度刺激や発熱物質の投与による反応に影響を与えるのかどうかを継時的に検討している。
    視索前野のEP3ニューロン群の細胞体の性質と神経終末の性質を詳細に解析することを継続するとともに、特定のEP3ニューロン群を神経活動操作法によってコントロールし、刺激応答がどのように変化するのかを、体温、褐色脂肪熱産生や摂食を指標にして解析する。また、交感神経活動なども合わせて解析する。

  3. Central circuit mechanisms underlying infection-induced symptoms

    Grant number:26860159  2014.4 - 2018.3

    Nakamura Yoshiko

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    Authorship:Principal investigator 

    Grant amount:\4030000 ( Direct Cost: \3100000 、 Indirect Cost:\930000 )

    Infection elicits a variety of central symptoms, such as fever, decreased appetite, and fatigue. However, the neural mechanisms underlying the infection-induced symptoms are unknown. In this study, I focused on preoptic area neurons that express prostaglandin EP3 receptors, which receive the pyrogenic mediator produced in response to infections. By using a technique to express reporter genes specifically in EP3 receptor-expressing neurons in the preoptic area, I revealed all the brain sites to which EP3 receptor-expressing preoptic neurons project their axons, and also electrophysiologically recorded activities of these neurons. Based on the data obtained from these analyses, I hypothesized that the medullary reticular neurons are involved in the infection-induced suppression of appetite. Further studies to test this hypothesis could lead to elucidation of the central neural circuit mechanisms of infection-induced symptoms.

  4. Multifaceted function analyses of fever-developing neurons using genetically modified rats

    Grant number:23790271  2011.4 - 2014.3

    NAKAMURA Yoshiko

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    Authorship:Principal investigator 

    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    To reveal the core brain mechanism of fever development, I have performed multifaceted analyses of prostaglandin EP3 receptor-expressing neurons in the preoptic area (EP3 neurons), a center for fever development. By creating a novel transgenic rat and viruses, I established a system that allows us to specifically transduce EP3 neurons with a reporter gene. Using this system, I transduced EP3 neurons with a membrane-targeted form of GFP to visualize their axon fibers, and thereby, successfully identified all the brain regions where EP3 neurons project their axons. Also, by illuminating EP3 neurons transduced with channelrhodopsin, I was able to change thermogenic activity of brown adipose tissue in anesthetized rats. I am currently doing electrophysiological analyses of EP3 neurons in brain slices.