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Mechanisms underlying glia-mediated ischemic tolerance

Research Project

Project/Area Number 25670622
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionUniversity of Yamanashi

Principal Investigator

KOIZUMI Schuichi  山梨大学, 総合研究部, 教授 (10280752)

Co-Investigator(Renkei-kenkyūsha) KINOUCHI Hiroyuki  山梨大学, 総合研究部, 教授 (30241623)
SHINOZAKI Youichi  山梨大学, 総合研究部, 講師 (10443772)
SHIGETOMI Eiji  山梨大学, 総合研究部, 助教 (00631061)
SHIBATA Keisuke  山梨大学, 総合研究部, 助教 (50580411)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsグリア細胞 / アストロサイト / 脳卒中 / 虚血耐性 / グリア伝達 / グリア / P2受容体 / 虚血 / P2X7受容体
Outline of Final Research Achievements

Using a preceding sub-lethal ischemic insult, preconditioning (PC), is an attractive strategy for protecting neurons by inducing ischemic tolerance in the brain. Although the underlying molecular mechanisms have been studied extensively, almost all experiments have been performed on neurons. Here, using a middle cerebral artery occlusion model in mice, we show that astrocytes have an essential role in the induction of ischemic tolerance. PC caused activation of astrocytes, which was essential for the induction of ischemic tolerance. As for the mechanisms, we found that P2X7 receptors were dramatically upregulated in activated astrocytes, which was essential for the ischemic tolerance. Unlike previous reports focusing on neuron-based mechanisms, our results show that astrocytes play indispensable roles in inducing ischemic tolerance.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (30 results)

All 2015 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 5 results,  Acknowledgement Compliant: 1 results) Presentation (22 results) (of which Invited: 4 results) Book (1 results)

  • [Journal Article] TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport2015

    • Author(s)
      Narita, K., Sasamoto, S., Koizumi, S. Okazaki, S., Nakamura, H., Inoue, T. and Takeda, S
    • Journal Title

      FASEB J

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term imipramine treatment increases N-methyl-d-aspartate receptor activity and expression via epigenetic mechanisms2015

    • Author(s)
      Nghia NA, Hirasawa T, Kasai H, Obata C, Moriishi K, Mochizuki K, Koizumi S, Kubota T.
    • Journal Title

      Eur J Pharmacol.

      Volume: 752C Pages: 69-77

    • DOI

      10.1016/j.ejphar.2015.02.010

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Astrocyte-Mediated Ischemic Tolerance2015

    • Author(s)
      Yuri Hirayama, Yuri Ikeda-Matsuo, Shoji Notomi, Hiroshi Enaida, Hiroyuki Kinouchi, Schuichi Koizumi
    • Journal Title

      Journal of Neuroscience

      Volume: 35(9) Issue: 9 Pages: 3794-3805

    • DOI

      10.1523/jneurosci.4218-14.2015

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] グリア伝達と脳の機能2015

    • Author(s)
      小泉修一
    • Journal Title

      日本神経精神薬理学雑誌

      Volume: 35 Pages: 5-9

    • Related Report
      2014 Annual Research Report
  • [Journal Article] ブシ 神経障害性疼痛2015

    • Author(s)
      小泉修一、柴田圭輔
    • Journal Title

      日本精神神経薬理学雑誌

      Volume: in press

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Expression of Astrocyte-Related Receptors in Cortical Dysplasia With Intractable Epilepsy.2014

    • Author(s)
      Sayuri Sukigara, Hongmei Dai, Shin Nabatame, Taisuke Otsuki, Sae Hanai, Ryoko Honda, Takashi Saito, Eiji Nakagawa, Takanobu Kaido, Noriko Sato, Yuu Kaneko, Akiko Takahashi, Kenji Sugai, Yuko Saito, Masayuki Sasaki, Yu-ichi Goto, Schuichi Koizumi,Masayuki Itoh
    • Journal Title

      J Neuropathol Exp Neurol

      Volume: 73(8) Issue: 8 Pages: 798-806

    • DOI

      10.1097/nen.0000000000000099

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of the P2Y1 receptor to hippocampal neuroinflammation and cognitive decline in a rodent model of focal cerebral stroke2013

    • Author(s)
      Chin Y, Kishi M, Sekino M, Nakajo F, Abe Y, Ohsaki H, Kato F, Koizumi S, Gac het C, Hisatsune T
    • Journal Title

      Journal of Neuroinflammation

      Volume: 26 Issue: 1 Pages: 10-95

    • DOI

      10.1186/1742-2094-10-95

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 脳虚血傷害後、活性化アストロサイトは貪食能を獲得する2015

    • Author(s)
      森澤 陽介, 平山友里, 小泉修一
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新しいグリア細胞機能:新可視化・操作法によりわかったグリアの新機能2015

    • Author(s)
      小泉修一
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-03-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] P2X7受容体/HIF-1α経路はアストロサイト依存的虚血耐性に特有なメカニズムである2015

    • Author(s)
      平山友里、松尾由理、小泉修一
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-03-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] アストロサイト依存的虚血耐性におけるP2X7受容体/HIF-1α経路の関与2014

    • Author(s)
      平山友里、松尾由理、小泉修一
    • Organizer
      第19回グリア研究会
    • Place of Presentation
      東京商工会議所(東京都)
    • Year and Date
      2014-12-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] 鍛えられるグリア細胞2014

    • Author(s)
      小泉修一、平山友里
    • Organizer
      第16回応用薬理シンポジウム
    • Place of Presentation
      松島大観荘(宮城県宮城郡)
    • Year and Date
      2014-12-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] グリア伝達とグリア性虚血耐性2014

    • Author(s)
      小泉修一
    • Organizer
      都医学研セミナー
    • Place of Presentation
      東京都医学総合研究所(東京都)
    • Year and Date
      2014-11-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Astrocytic phagocytosis after brain ischemia2014

    • Author(s)
      Schuichi Koizumi
    • Organizer
      KIST国際シンポジウム
    • Place of Presentation
      Soul(Korea)
    • Year and Date
      2014-10-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 脳虚血障害後、活性化アストロサイトは貪食能を獲得する2014

    • Author(s)
      森澤陽介
    • Organizer
      平成26年度生理学研究所研究会
    • Place of Presentation
      生理学研究所(愛知県岡崎市)
    • Year and Date
      2014-10-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Astrocytes and Ischemic tolerance2014

    • Author(s)
      Schuichi Koizumi
    • Organizer
      Conference on Glial Biology in Medicine
    • Place of Presentation
      Birmingham(U.S.A)
    • Year and Date
      2014-10-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] アストロサイト依存的虚血耐性の分子メカニズム解析2014

    • Author(s)
      平山友里、松尾由理、小泉修一
    • Organizer
      第131回日本薬理学会関東部会
    • Place of Presentation
      横浜市立大学(神奈川県横浜市)
    • Year and Date
      2014-10-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] P2X7受容体依存型虚血耐性のメカニズム解析2014

    • Author(s)
      平山友里、松尾由理、小泉修一
    • Organizer
      第57回日本神経化学会大会・第36回日本生物学的精神医学会合同大会
    • Place of Presentation
      奈良県文化会館(奈良県奈良市)
    • Year and Date
      2014-09-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Ischemic tolerance mediated by the glia purinergic system2014

    • Author(s)
      Schuichi Koizumi,
    • Organizer
      Purine2014
    • Place of Presentation
      Bonn(Germany)
    • Year and Date
      2014-07-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] Astrocyte-Mediated ischemic tolerance in the brain2014

    • Author(s)
      Y Hirayama, Y Ikeda-Matsuo, S Koizumi
    • Organizer
      9th FENS Forum of Neuroscience
    • Place of Presentation
      Milan(Italy)
    • Year and Date
      2014-07-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] グリア細胞と脳虚血耐性2014

    • Author(s)
      小泉修一
    • Organizer
      第2回パーキンソン病と神経科学研究会
    • Place of Presentation
      ANAクラウンプラザホテル(京都府京都市)
    • Year and Date
      2014-06-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 脳機能を制御する新しい役者・グリア細胞2014

    • Author(s)
      小泉修一
    • Organizer
      第29回インターゲノミクスセミナー
    • Place of Presentation
      神戸大学(兵庫県神戸市)
    • Year and Date
      2014-06-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 脳虚血障害のグリア性制御2014

    • Author(s)
      小泉修一、平山友里
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      東北大学百周年記念会館(仙台市)
    • Related Report
      2013 Research-status Report
  • [Presentation] グリア性脳虚血耐性現象の分子メカニズム解析2013

    • Author(s)
      平山 友里、松尾 由理、 小泉 修一
    • Organizer
      平成25年度日本生化学会関東支部例会
    • Place of Presentation
      山梨大学(山梨県中央市)
    • Related Report
      2013 Research-status Report
  • [Presentation] アストロサイト依存型虚血耐性のメカニズム2013

    • Author(s)
      平山友里、松尾由理、小泉修一
    • Organizer
      Neuro2013
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2013 Research-status Report
  • [Presentation] アストロサイトによるシナプス再編2013

    • Author(s)
      小泉修一
    • Organizer
      Neuro2013
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 脳虚血障害後、活性化アストロサイトは貪食性を呈する2013

    • Author(s)
      森澤陽介、平山友里、芝田晋介、岡野栄之、小泉修一
    • Organizer
      Neuro2013
    • Place of Presentation
      国立京都国際会館(京都市)
    • Related Report
      2013 Research-status Report
  • [Presentation] Microglial ATP exocytosis and its pathophysiological consequences.2013

    • Author(s)
      小泉修一
    • Organizer
      XI European Meeting on glial cells in Health and Disease
    • Place of Presentation
      Estrel Berlin(Berlin)
    • Related Report
      2013 Research-status Report
  • [Presentation] Mechanisms underlying astrocyte-dependent ischemic tolerance.2013

    • Author(s)
      平山友里、松尾由理、小泉修一
    • Organizer
      Neuroscience2013
    • Place of Presentation
      San Diego Convention Center(San Diego)
    • Related Report
      2013 Research-status Report
  • [Book] 最新臨床脳卒中学(上)2014

    • Author(s)
      小泉修一
    • Total Pages
      4
    • Publisher
      日本臨床
    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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