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Neural activity-dependent transcription factor Npas4 is required for neuroprotection and survival after stroke

Research Project

Project/Area Number 18K06465
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionKagawa University

Principal Investigator

Hiroo Takahashi  香川大学, 医学部, 助教 (20390685)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsNpas4 / 脳梗塞 / 細胞死 / 転写因子
Outline of Final Research Achievements

Cerebral infarction is an extremely common disease. This study analyzed the endogenous neuroprotective mechanism activated by cerebral infarction. We found that the transcription factor Npas4, which is known to promote neuronal development in a healthy brain, is strongly induced in cerebral cortical neurons after infarction. Analysis using Npas4-deficient mice and adeno-associated virus revealed that Npas4 plays a role in suppressing cell death in infarct lesions and maintaining prognostic motor function. Npas4 expression was induced by abnormal Ca2+ influx into ischemic neurons. Npas4 reduces Ca2+ influx and facilitates cell survival after infarction. These results suggest that Npas4 acts as a negative regulator of Ca2+ influx in ischemic neurons.

Academic Significance and Societal Importance of the Research Achievements

脳梗塞は発生頻度の高い疾患であり、多くの寝たきりを産んでいる。本研究の成果により、脳梗塞で発現が誘導される転写因子Npas4は、脳梗塞による細胞死を防ぐための、内在性の神経保護メカニズムに必須の因子であることが明らかとなった。今後、Npas4が虚血時のニューロンにおいて細胞死を防ぐメカニズムの詳細を明らかとすれば、その経路を人工的に活性化することも可能となり、新たな脳梗塞の治療や予防に繋がると期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Expression of Oncofetal Antigen 5T4 in Murine Taste Papillae.2019

    • Author(s)
      Takahashi Y, Takahashi H*, Stern PL, Kirita T, Tsuboi A*
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 13 Pages: 343-343

    • DOI

      10.3389/fncel.2019.00343

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 内在性の神経回路再編機構の理解に基づく革新的な脳梗塞治療法の開発2019

    • Author(s)
      坪井昭夫, 高橋弘雄
    • Journal Title

      Medical Science Digest

      Volume: 45 Pages: 22-24

    • Related Report
      2018 Research-status Report
  • [Journal Article] The functional role of olfactory bulb granule cell subtypes derived from embryonic and postnatal neurogenesis.2018

    • Author(s)
      Takahashi H, Yoshihara S and Tsuboi A.
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 11

    • DOI

      10.3389/fnmol.2018.00229

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Ras-like Gem GTPase induced by Npas4 promotes activity-dependent tolerance for ischemic stroke2020

    • Author(s)
      高橋弘雄
    • Organizer
      NEURO2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経活動依存的な転写因子Npas4は脳梗塞に伴う細胞死を抑制する2019

    • Author(s)
      高橋弘雄
    • Organizer
      NEURO2019
    • Related Report
      2019 Research-status Report
  • [Presentation] MDGAファミリー分子群の欠失が引き起こすE/I バランス偏移に伴う認知・行動異常の解析2019

    • Author(s)
      Razib Hossain, 多田 篤史, 黒川 直弘, 長澤 研, 琢磨 和晃, 尾嶋 大喜, 高橋 弘雄, 岸本泰司, 山本 融
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 嗅球における介在ニューロンのサブタイプの機能的な役割2018

    • Author(s)
      高橋弘雄
    • Organizer
      2018年度日本味と匂学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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