2012 Fiscal Year Final Research Report
Research on the pathophysiological roles of TRP channels on the neuron-glia interactions in central nervous system disorder
| Project/Area Number |
21390022
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
KANEKO Shuji 京都大学, 大学院・薬学研究科, 教授 (60177516)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Takayuki 京都大学, 大学院・薬学研究科, 准教授 (30303845)
SHIRAKAWA Hisashi 京都大学, 大学院・薬学研究科, 助教 (50402798)
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| Project Period (FY) |
2009 – 2012
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| Keywords | TRPチャネル / TRPV4 / TRPC3 / TRPM2 / アストロサイト / ミクログリア / 細胞内カルシウム動態 / 中枢神経変性疾患 |
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| Research Abstract |
The importance of interactions between neurons and glia in the pathogenesis of CNS disorders is becoming revealed and understood; however the pathophysiological roles of TRP channels in neuron-glia signaling remain to be elucidated. This study focused on TRPC3 expressed in astrocyte and TRPV4 and TRPM2 expressed in microglia. In vitro and in vivo experiments demonstrate that 1) TRPC3 inhibitor Pyr3 improves outcomes and attenuates astrogliosis after intracerebral hemorrhage in mice, 2) the opening of TRPV4 channel attenuates the driving force for extracellular Ca2+ and suppresses microglial activation, 3) TRPM2 could mediate the cerebral ischemic injury through NO release from macrophage/microglia. These results suggest that the above-mentioned TRP channelsmay constitute a new therapeutic target for CNS disorders.
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[Journal Article] Stimulation of transient receptor potential vanilloid 4 channel suppresses abnormal activation of microglia induced by lipopolysaccharide2012
Author(s)
Konno M, Shirakawa H, lida S, Sakimoto S, Matsutani I, Miyake T,Kageyama K, Nakagawa T, Shibasaki K, Kaneko, S.
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Journal Title
Glia
Volume: 60
Pages: 761-770
DOI
Peer Reviewed
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[Journal Article] TRPC3 mediates thrombin-induced astrocyte activation and upregulates its own expression in rat cortical astrocytes2010
Author(s)
Shirakawa H, Sakimoto S, Nakao K, Sugishita A, Konno M, Iida S, Kusano A, Hashimoto E, Nakagawa T, Kaneko, S
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Journal Title
Journal of Neuroscience
Volume: 30
Pages: 13116-13129
DOI
Peer Reviewed
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