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Post-translational modification-based molecular mechanisms in the brain involved in recovery of paralysis after cerebral infarction.

Research Project

Project/Area Number 17K01483
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Rehabilitation science/Welfare engineering
Research InstitutionFujita Health University

Principal Investigator

Kenmei Mizutani  藤田医科大学, 医療科学部, 准教授 (30351068)

Co-Investigator(Kenkyū-buntansha) 脇田 英明  藤田医科大学, 医学部, 教授 (80416172)
Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords脳梗塞 / リハビリテーション / 麻痺回復 / 脳内分子機構 / 薬剤投与 / 神経可塑性 / 分子機構
Outline of Final Research Achievements

The results of a phospho-proteome analysis of peripheral infarcted cortex, in which functional recovery was observed after training after inducing infarction in rats, suggested the involvement of cAMP signaling pathways, MAPK signaling pathways, and others. The analysis of kinases with altered phosphorylation in these pathways revealed 15 kinases. The combination of bryostatin-1, an activator of PKC, and exercise training resulted in inhibition of GSK3βSer9 phosphorylation, which is located downstream of PKC, and inhibition of CRMP2 phosphorylation. It was speculated that inhibition of CRMP2 phosphorylation induces axonal elongation by microtubule polymerization. The effect of bryostatin in combination with training appears to be mediated via PKC phosphorylation, with effects on functional recovery occurring through the downstream regulation of GSK3β and CRMP2 phosphorylation.

Academic Significance and Societal Importance of the Research Achievements

近年、脳卒中後の麻痺や障害に対して、脳の可塑性変化に基づいた新たなリハビリテーションという概念が浸透し始め、積極的に麻痺回復を行う治療戦略に関心が高まりつつあるが、実際、脳内では何が生じて麻痺回復に繋がっているのか不明である。そこで、脳卒中リハビリテーションの麻痺回復に関連した分子機構をタンパクのリン酸化網羅的解析によりターゲット分子を特定し、さらにProtein kinase C(PKC)の活性化剤を投与することにより、訓練単独より更なる運動機能のが認められた。PKCの下流に位置する分子機構についても解析を行い分子の相互作用についても明らかにした。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (6 results)

All 2021 2020 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (4 results)

  • [Journal Article] Selective accumulation of adiponectin in the cerebral cortex under chronic cerebral hypoperfusion in the rat.2020

    • Author(s)
      Takahashi Y, Wakita H, Mizutani K, Watanabe A, Sonoda S, Tomimoto H.
    • Journal Title

      Neuroreport.

      Volume: 31 Issue: 2 Pages: 148-155

    • DOI

      10.1097/wnr.0000000000001391

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ritanserin, a serotonin-2 receptor antagonist, inhibits functional recovery after cerebral infarction.2018

    • Author(s)
      Mizutani K, Sonoda S, Wakita H
    • Journal Title

      NeuroReport

      Volume: 29 Issue: 1 Pages: 54-58

    • DOI

      10.1097/wnr.0000000000000930

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 脳梗塞モデルラットへの訓練効果と脳内リン酸化プロテオーム解析による分子機構の解明2021

    • Author(s)
      水谷謙明 園田茂 脇田英明
    • Organizer
      第127回日本解剖学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脳梗塞ラットへの訓練・薬剤併用療法の効果と脳内分子機構について2019

    • Author(s)
      水谷謙明、園田 茂、脇田英明
    • Organizer
      Brain and Rehabilitation 2019 ・第26回脳機能とリハビリテーション研究会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 脳梗塞ラットへの訓練・薬剤併用療法と脳内リン酸化タンパクの変動2019

    • Author(s)
      水谷謙明、園田 茂、脇田英明
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脳梗塞ラットにおける訓練効果と脳内セロトニンの役割2018

    • Author(s)
      水谷 謙明、園田 茂、脇田英明
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2023-01-30  

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