Research on the new pathophysiological roles of TRPV channel that could regulate the activation of brain cells

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790519
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Applied pharmacology
• Research Institution: Kyoto University
• Principal Investigator: SHIRAKAWA Hisashi 京都大学, 大学院・薬学研究科, 助教 (50402798)
• Co-Investigator(Renkei-kenkyūsha): KANEKO Shuji 京都大学, 大学院・薬学研究科, 教授 (60177516) ; NAKAGAWA Takayuki 京都大学, 大学院・薬学研究科, 准教授 (30303845)
• Project Period (FY): 2009 – 2010
• Keywords: ミクログリア / TRPチャネル / TRPV4 / カリウムチャネル / 電気生理学 / 細胞内カルシウム動態 / TNF-α / 中枢神経変性疾患

Research Abstract

Microglia are intrinsic immune cells in the brain. In response to neurodegenerative diseases, excessively activated microglia change their shapes and release various cytokines involved in the pathogenesis of CNS disease. This study focused on TRPV4 channel expressed in microglia. In vitro and in vivo experiments demonstrate that the depolarization in response to the opening of TRPV4 channel attenuates the driving force for extracellular Ca2+ and suppresses microglial activation.

Research Products

• [Journal Article] Repeated exposure to methamphetamine, cocaine or morphine induces augmentation of dopamine release in rat mesocorticolimbic slice co-culture (2011)
  • Author(s): Nakagawa T, Suzuki T, Nagayasu T, Kitaichi M, Shirakawa H, Kaneko S.
  • Journal Title: PLoS One Volume: 6 Pages: e24865
  • DOI: DOI:10.1371/journal.pone.0024865.
  • Peer Reviewed
• [Journal Article] TRPC3 mediates thrombin-induced astrocyte activation and upregulates its own expression in rat cortical astrocytes (2010)
  • Author(s): Shirakawa H, Sakimoto S, Nakao K, Sugishita A, Konno M, Iida S, Kusano A, Hashimoto E, Nakagawa T, Kaneko, S.
  • Journal Title: Journal of Neuroscience Volume: 30 Pages: 13116-13129
  • DOI: DOI:10.1523/JNEUROSCI.1890-10.2010.
  • Peer Reviewed
• [Presentation] Stimulation of TRPV4 channel suppresses aberrant activation of microglia induced by lipopolysaccharide (2011)
  • Author(s): Konno M, Shirakawa H, 他5名
  • Organizer: The 6th SKO Symposium
  • Place of Presentation: ソウル(韓国)
  • Year and Date: 2011-06-02
• [Presentation] リポ多糖誘発ミクログリア異常活性化に対するTRPV4開口刺激による抑制作用 (2011)
  • Author(s): 金野真和、白川久志、他4名
  • Organizer: 日本薬学会第131回年会
  • Place of Presentation: ツインメッセ静岡(静岡県)誌上開催
  • Year and Date: 2011-03-29
• [Presentation] TRPチャネルによる脳内グリア細胞の新しい活性調節機構 (2011)
  • Author(s): 白川久志、他2名
  • Organizer: 日本薬学会第131回年会
  • Place of Presentation: ツインメッセ静岡(静岡県)誌上開催
  • Year and Date: 2011-03-29
• [Presentation] TRPV4開口によるミクログリア異常活性化抑制及びそのメカニズムの解析 (2010)
  • Author(s): 金野真和、白川久志、他4名
  • Organizer: 薬理系薬学会次世代シンポジウム2010
  • Place of Presentation: 京都大学薬学部(京都府)
  • Year and Date: 2010-09-11
• [Remarks]
  • URL: http://www.pharm.kyoto-u.ac.jp/channel/ja/research/index.html
• [Remarks]
  • URL: http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2010/100930_1.htm