| Project/Area Number |
17K01483
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Rehabilitation science/Welfare engineering
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| Research Institution | Fujita Health University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
脇田 英明 藤田医科大学, 医学部, 教授 (80416172)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| 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)
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| 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 |
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| 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.
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| 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。
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