Mechanisms of synaptic plasticity mediated by glia

2008 Fiscal Year Final Research Report

• Project/Area Number: 17300124
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: University of Yamanashi (2006-2008); National Institute of Health Sciences (2005)
• Principal Investigator: KOIZUMI Schuichi University of Yamanashi, 大学院・医学工学総合研究部, 教授 (10280752)
• Co-Investigator(Kenkyū-buntansha): FUJISHITA Kayoko 山梨大学, 大学院・医学工学総合研究部, 助教 (10443102) ; KATAOKA Yasufumi , 福岡大学・薬学部, 教授 (70136513)
• Co-Investigator(Renkei-kenkyūsha): OKUBO Satoko 国立医薬品食品衛生研究所, 研究員 (20274954)
• Project Period (FY): 2005 – 2008
• Keywords: グリア細胞 / アストロサイト / ATP / P2 受容体 / 可塑性 / 海馬

Research Abstract

これまで『脳の可塑性研究』は、『シナプスの可塑性研究』として行われてきた。しかし非常に変化し易く、また脳内で最大数を占める『アストロサイト』の可塑性がシナプスの可塑性に影響することを示した。生理的条件下でも、また病態生理的条件下でも、アストロサイトはその性質を可塑的に変化させ、それがシナプス可塑性変化と強くリンクしていた。この分子メカニズムには、アストロサイトのATP 受容体を介するシグナル変化が強く関連していた。

Research Products

• [Journal Article] Direct observation of ATP-induced conformational changes in single P2X_4 receptors (2009)
  • Author(s): Shinozaki, Y., Sumitomo, K., Tsuda, M., Koizumi, S., Inoue, K. and Torimitsu, K.
  • Journal Title: PLoS Biology, in press
  • Peer Reviewed
• [Journal Article] Grape seed extract (GSE) acting on astrocytes, reveals its neuronal protection against oxidative stress via interleukin-6 mediated mechanisms (2009)
  • Author(s): Fujishita, K., Ozawa, T., Shibata, K., Tanabe, S., Sato, Y., Hisamoto, M., Okuda, T. and Koizumi, S.
  • Journal Title: Cell Mol Neurobiol (in press)
  • Peer Reviewed
• [Journal Article] Fibronectin/integrin system is involved in P2X(4) receptor upregulation in the spinal cord and neuropathic pain after nerve injury (2008)
  • Author(s): Tsuda, M., Toyomitsu T., Komatsu T. Masuda T., Kunifusa E., Nasu-Tada K., Koizumi S., Yamamoto K., Ando J. and Inoue, K.
  • Journal Title: Glia 56 Pages: 579-585
  • Peer Reviewed
• [Journal Article] Reduced pain behaviors and extracellular signal-related protein kinase activation in primary sensory neurons by peripheral tissue injury in mice lacking platelet-activating factor receptor (2007)
  • Author(s): Tsuda M, Ishii S, Masuda T, Hasegawa S, Nakamura K, Nagata K, Yamashita T, Furue H, Tozaki-Saitoh H, Yoshimura M, Koizumi S, Shimizu T, Inoue K.
  • Journal Title: J. Neurochem 102 Pages: 1658-1668
• [Journal Article] Retinoic acids acting through retinoid receptors protect hippocampal neurons from oxygen-glucose deprivation-mediated cell death by inhibition of c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase (2007)
  • Author(s): Shinozaki, Y., Sato, Y., Koizumi, S., Ohno, Y., Nagao, T, Inoue, K.
  • Journal Title: Neurosci. 147 Pages: 153-163
• [Journal Article] UDP acting at P2Y6 receptors is a novel mediator of microglial phagocytosis (2007)
  • Author(s): Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., Joshi, B.V., Jacobson, K.A., Kohsaka, S. and Inoue, K.
  • Journal Title: Nature 446 Pages: 1091-1095
  • Peer Reviewed
• [Journal Article] Upregulation by retinoic acid of P2Y2 receptors in normal human epidermal keratinocytes (2006)
  • Author(s): Fujishita, K., Koizumi, S. and Inoue, K.
  • Journal Title: Purinergic Signaling 2 Pages: 491-498
  • Peer Reviewed
• [Journal Article] Possible involvement of increase in spinal fibronectin following peripheral nerve injury in upregulation of microglial P2X4 (2006)
  • Author(s): Nasu-Tada, K., Koizumi, S., Tsuda, M., Kunifusa, E. and Inoue, K.
  • Journal Title: a key molecule for mechanical allodynia. Glia 53(*equal contribution) Pages: 769-775
  • Peer Reviewed
• [Journal Article] Retinoic acids increase P2X2 receptor expression through the 5'-flanking region of P2rx2 gene in rat phaeochromocytoma PC12 cells (2006)
  • Author(s): Tozaki-Saito, H., Koizumi, S., Sato, Y., Tsuda, M., Nagao, T. and Inoue, K.
  • Journal Title: Mol. Pharmacol 70(1) Pages: 319-328
  • Peer Reviewed
• [Journal Article] Activation of P2Y1 receptors in astrocytes interferes the H2O2 evoked death promoting signaling cascades (2006)
  • Author(s): Shinozaki, T., Koizumi, S., Ohno, T., Nagao, T. and Inoue, K.
  • Journal Title: Glia 54(6) Pages: 606-618
  • Peer Reviewed
• [Journal Article] Cytoprotection against oxidative-stress-induced damage of astrocytes by extracellular ATP via P2Y1 receptors (2005)
  • Author(s): Shinozaki, Y., Koizumi, S., Ishida, S., Sawada, J., Ohno, Y. and Inoue, K.
  • Journal Title: Glia 49 Pages: 288-300
  • Peer Reviewed
• [Journal Article] Characterization of multiple P2X receptors in cultured normal human epidermal keratinocytes (2005)
  • Author(s): Inoue, K., Denda, M., Tozaki, H., Fujishita, K., Koizumi, S. and Inoue, K.
  • Journal Title: J. Invest. Dermatol. 124 Pages: 756-763
  • Peer Reviewed
• [Journal Article] Long-lasting change in brain dynamics induced by methamphetamine: enhancement of protein kinase C-dependent astrocytic response and behabioral sensitization (2005)
  • Author(s): Narita, M., Miyatake, M., Shibasaki, M., Tsuda, M., Koizumi, S., Narita, M., Yajima, Y., Inoue, K. and Suzuki, T.
  • Journal Title: J. Neurochem. 93 Pages: 1383-1392
  • Peer Reviewed
• [Journal Article] The involvement of R1 integnin in microglial chemotaxis and proliferation on fibronectin:different regulations by ADP through PKA (2005)
  • Author(s): Nasu-tada, K., Koizumi, S. and Inoue, K.
  • Journal Title: Glia 52 Pages: 98-107
  • Peer Reviewed
• [Journal Article] 2006)ATP を介した皮膚ケラチノサイト間情報連絡と痛み、Pain Research
  • Author(s): 小泉修一、藤下加代子、津田誠、井上和秀
  • Journal Title: 21 Pages: 133-139
  • Peer Reviewed
• [Presentation] Astrocyte-to-neuron communications mediated by extracellular ATP (2009)
  • Author(s): Koizumi, S., Fujishita, K.
  • Organizer: 第129回日本薬学会
  • Year and Date: 20090326-28
• [Presentation] Glial function and ischemic brain injury.(シンポジウム) (2009)
  • Author(s): Koizumi, S., Fujishita, K.
  • Organizer: 第82回日本薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 20090316-18
• [Presentation] Mechanisms underlying upregulation of P2Y_6 receptors in microglia in kainate-induced injury model (2009)
  • Author(s): Fujishita, K., Nakao, A., Koizumi, S.
  • Organizer: 第82回日本薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 20090316-18
• [Presentation] Microglial proliferation mediated by P2Y_2 receptors after kainate-induced neuronal injury (2009)
  • Author(s): Tanaka, Y., Fujishita, K. and Koizumi, S.
  • Organizer: 第82回日本薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 20090316-18
• [Presentation] Antidepressants increase BDNF in astrocytes (2009)
  • Author(s): Ozawa, T., Fujishita, K., Shibata, K and Koizumi, S.
  • Organizer: 第82回日本薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 20090316-18
• [Presentation] Analgesic effect of Bushimatsu on neuropathic pain (2009)
  • Author(s): Shibata K, Sugawara, K, Fujishita K, Ozawa T, Matsukawa T, Suzuki T & Koizumi S.
  • Organizer: 第82回日本薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 20090316-18
• [Presentation] Astrocyte-to-pericyte communication mediated by ATP (2008)
  • Author(s): Fujishita, K., Sueishi, K., Takata, F., Kataoka, Y. & Koizumi, S.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington DC
  • Year and Date: 20081115-19
• [Presentation] アストロサイトによるATP情報発信 (2008)
  • Author(s): 小泉修一、藤下加代子
  • Place of Presentation: 岡崎生理研究会
  • Year and Date: 20080904-05
• [Presentation] Microglial nucleotide sensor P2Y6 receptors and brain functions (2008)
  • Author(s): Koizumi, S., Shigemoto-Mogami, Y., Kaoru, T., Shinozaki, Y., Fujishita, K., Ohsawa, K., Tsuda, M., Kohsaka, S. and Inoue, K.
  • Organizer: 第31回日本神経科学会
  • Year and Date: 20080709-11
• [Presentation] The "eat-me signal UDP" and microglial phagocytosis mediated by P2Y6 receptors (2008)
  • Author(s): Koizumi, S., Shigemoto-Mogami, Y., Shinozaki, Y., Ohsawa, K., Tsuda, M., Jacobson, K., Kohsaka, S. and Inoue, K
  • Organizer: 日米グリアシンポジウム
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 20080318-20
• [Presentation] The "eat-me signal UDP" and microglialphagocytosis.(シンポジウム) (2008)
  • Author(s): Koizumi, S., Shigemoto-Mogami, Y., Shinozaki, Y., Ohsawa, K., Tsuda, M., Jacobson, K., Kohsaka, S. and Inoue, K.
  • Organizer: 第81回日本薬理学会
  • Year and Date: 20080317-19
• [Presentation] Upregulation of M1 muscarinic actylcholine receptor in hippocampal neurons by astrocytic ATP (2008)
  • Author(s): Koizumi, S., Shigemoto-Mogami, Y., Shinozaki, Y., Ohsawa, K., Tsuda, M., Jacobson, K., Kohsaka, S. and Inoue, K
  • Organizer: 第81回日本薬理学会
  • Year and Date: 20080317-19
• [Presentation] グリア細胞による脳機能の制御 (2008)
  • Author(s): 小泉修一
  • Organizer: 第20回山梨神経科学研究会
  • Place of Presentation: 山梨
  • Year and Date: 2008-11-25
• [Presentation] ミクログリアP2Y6 受容体発現亢進の分子メカニズム (2008)
  • Author(s): 藤下加代子、中尾篤人、小泉修一
  • Organizer: グリア研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-11-08
• [Presentation] Extracellular nucleotides regulate two different microglial functions (2008)
  • Author(s): Koizumi, S
  • Organizer: i.e., phagocytosis and chemotaxis,OIST symposium
  • Place of Presentation: 沖縄
  • Year and Date: 2008-04-18
• [Presentation] 細胞外ヌクレオチドセンサーP2Y6 受容体とミクログリアの貪食(シンポジウム) (2007)
  • Author(s): Koizumi, S., Shigemoto-Mogami, Y., Shinozaki, Y., Ohsawa, K., Tsuda, M., Jacobson, K., Kohsaka, S. and Inoue, K
  • Organizer: 日本生化学・分子生物学合同大会
  • Year and Date: 20071211-15
• [Presentation] UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis (2007)
  • Author(s): Shinozaki, Y., Ohsawa, K., Tsuda, M., Jacobson, K., Kohsaka, S. and Inoue, K
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 20071103-05
• [Presentation] Micorglial phagocytosis mediated by P2Y6 receptors (2007)
  • Author(s): Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., Jacobson, K., Kohsaka, S. and Inoue, K.
  • Organizer: The 2^<nd> Joint Italian-German Purine Club Meeting
  • Place of Presentation: Leipzig, Germany
  • Year and Date: 20070912-15
• [Presentation] 細胞外ヌクレオチドを介した損傷神経細胞-グリア細胞連関 (2007)
  • Author(s): 小泉修一、重本(最上)由香里、多田薫、篠崎陽一、大澤圭子、津田誠、高坂新一、井上和秀
  • Organizer: 生理研研究会
  • Place of Presentation: 岡崎
  • Year and Date: 20070906-07
• [Presentation] A new pharmacological profile of microglial P2Y receptors (Symposium) (2007)
  • Author(s): Koizumi, S
  • Organizer: The 3^<rd> China-Japan Join Meeting of Basic and Clinical Pharmacology
  • Place of Presentation: Dalian, China
  • Year and Date: 20070823-24
• [Presentation] Tonic and wide-ranging regulation of neurons by gliotransmitters (2007)
  • Author(s): Koizumi, S., Fujishita, K. and Inoue, K
  • Organizer: 第84回日本生理学会(シンポジウム)
  • Place of Presentation: 大阪
  • Year and Date: 20070320-22
• [Presentation] Glial P2 receptors are attractive targets for drug discovery (2007)
  • Author(s): Koizumi, S., Shinozaki, Y., Nasu-Tada, K. and Inoue, K
  • Organizer: (シンポジウム) 第80回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20070314-16
• [Presentation] Upregulation by astrocytic ATP of M1 muscarinic actylcholine receptor in hippocampal neurons (2007)
  • Author(s): Fujishita, K., & Koizumi, S.
  • Organizer: 第80回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20070314-16
• [Presentation] Enhancement of P2Y6 receptor-mediated signaling by lipopolysaccharide in rat hippocampal astrocytes. (2007)
  • Author(s): Ohkubo, S., Koizumi, S.
  • Organizer: 第80回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20070314-16
• [Presentation] Adenosine enhances fluoxetine-induced BDNF production in rat hippocampal astrocytes (2007)
  • Author(s): Suto, K., Ohkubo, S., Honda, K. and Koizumi, S.
  • Organizer: 第80回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20070314-16
• [Presentation] 、中枢神経傷害時の細胞外ヌクレオチドとミクログリアの貪食作用 (2007)
  • Author(s): 小泉修一、重本(最上)由香里、多田薫、篠崎陽一、大澤圭子、津田誠、高坂新一、井上和秀(シンポジウム)
  • Organizer: グリア研究会
  • Year and Date: 2007-11-17
• [Presentation] "Eat-me signal" UDP とミクログリアの貪食作用 (2007)
  • Author(s): 小泉修一
  • Organizer: 名古屋大学COE シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2007-06-07
• [Presentation] 中枢神経傷害時の細胞外ヌクレオチドとミクログリアの貪食作用(シンポジウム) (2007)
  • Author(s): 小泉修一、重本由香里、多田薫、篠崎陽一、大澤圭子、津田誠、高坂新一、井上和秀
  • Organizer: 第4回GPCR 研究会
  • Place of Presentation: 東京
  • Year and Date: 2007-05-11
• [Presentation] Glia-to-vascular communication mediated by extracellular ATP (Symposium) (2006)
  • Author(s): Koizumi, S., Fujishita, K. and Inoue, K.
  • Organizer: 第48回日本神経化学会
  • Place of Presentation: Fukuoka
  • Year and Date: 20061028-30
• [Presentation] Synthesis and secretion of MMP-9 by inhibition of P2Y receptors in astrocytes (2006)
  • Author(s): Koizumi, S., Nasu-Tada, K., Inoue, K
  • Organizer: Society for Neuroscience Meeting
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20061014-18
• [Presentation] Lipopolysaccharide alters P2Y receptor-mediated signaling in rat astrocytes via RGS-mediated mechanisms (2006)
  • Author(s): Ohkubo, S. and Koizumi, S
  • Organizer: Society for Neuroscience Meeting
  • Place of Presentation: Atlanta, USA
  • Year and Date: 20061014-18
• [Presentation] Absence of P2Y signal induces astrocytes to release TNF-alpha, which provides autocrine regulation of MMP-9 (2006)
  • Author(s): 小泉修一、多田薫、井Koizumi, S., Nasu-Tada, K. Inoue, K
  • Organizer: 第49回日本神経化学会
  • Year and Date: 20060914-16
• [Presentation] Involvement of spinal fibronectin in upregulation of microglial P2X4, a key molecule for mechanical allodynia (2006)
  • Author(s): Koizumi, S., Nasu-Tada, K., Tsuda, M., Kunifusa, E. and Inoue, K
  • Organizer: 日本神経科学会
  • Place of Presentation: 京都
  • Year and Date: 20060719-21
• [Presentation] Intimate interaction mediated by P2Y_2 receptors between astrocytes and pericytes (2006)
  • Author(s): Koizumi, S., Fujishita, K. Sueishi, K., Kataoka, Y., Ohkubo, S. and Inoue, K.
  • Organizer: 8^<th> ISAAN
  • Place of Presentation: Ferrara, Italy
  • Year and Date: 20060524-28
• [Presentation] Upregulation of P2Y2 receptors by retinoids in normal human epidermal keratinocytes (2006)
  • Author(s): Fujishita, K., Inoue, K. and Koizumi, S
  • Organizer: 8^<th> ISAAN
  • Place of Presentation: Ferrara, Italy
  • Year and Date: 20060524-28
• [Presentation] ATP 受容体を介するアストロサイトーペリサイト系による毛細血管制御(シンポジウム) (2006)
  • Author(s): 小泉修一、藤下加代子、末石浩二、高田芙友子、片岡泰文
  • Organizer: 第79回日本薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 20060308-10
• [Presentation] 血管周費細胞ペリサイトに発現するP2 受容体の生理的役割 (2006)
  • Author(s): 藤下加代子、末石浩二、片岡泰文、井上和秀、小泉修一
  • Organizer: 第79回日本薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 20060308-10
• [Presentation] ラットアストロサイトにおけるリポポリサッカライドによるP2 受容体シグナルの変化 (2006)
  • Author(s): 大久保聡子、多田薫、斉藤秀俊、小泉修一
  • Organizer: 第79回日本薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 20060308-10
• [Presentation] アストロサイトのP2Y 受容体抑制によるMMP-9産生と放出 (2006)
  • Author(s): 井上和秀
  • Organizer: 第11回グリア研究会
  • Place of Presentation: 東京
  • Year and Date: 2006-11-11
• [Presentation] アストロサイトの機能変化とシナプス伝達の可塑性 (2006)
  • Author(s): 小泉修一
  • Organizer: 生理研シンポジウム
  • Place of Presentation: 岡崎
  • Year and Date: 2006-05-24
• [Presentation] Mechanical allodynia induced by P2Y2 receptor activation (2005)
  • Author(s): Koizumi, S., Tsuda, M. & Inoue, K
  • Organizer: Society for Neuroscience, Washington DC
  • Year and Date: 20051112-16
• [Presentation] Astrocytes function as an interface of neurovascular system (Symposium) (2005)
  • Author(s): Koizumi, S
  • Place of Presentation: vTokyo
  • Year and Date: 20050726-28
• [Presentation] Dynamic astrocyte-to-neuron communication mediated by astrocytic ATP in hippocampal cultures (2005)
  • Author(s): Koizumi, S. and Inoue, K
  • Organizer: Euroglia Meeting
  • Place of Presentation: Amsterdam, Holland
  • Year and Date: 20050517-21
• [Presentation] アストロサイトによるシナプス伝達制御(シンポジウム) (2005)
  • Author(s): 小泉修一、大野泰雄、井上和秀
  • Organizer: 日本薬理学会関東部会
  • Place of Presentation: 東京
  • Year and Date: 2005-06-18
• [Book] Brain and Nerve(56) (2007)
  • Author(s): 小泉修一、藤下加代子
  • Total Pages: 707-715
  • Publisher: アストロサイトを介したニューロン・アストロサイト相互調節
• [Book] ブレインサイエンス・レビュー2006(伊藤正男、川合述史編) (2006)
  • Author(s): 小泉修一
  • Total Pages: 105-120
  • Publisher: グリア細胞によるシナプス伝達制御に関する研究
• [Remarks] 『グリア細胞による脳機能の制御』2009年3月
• [Remarks] 日本学士院学術奨励賞『グリア細胞による脳機能の制御』2009 年3月