| Project/Area Number |
18K19720
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2018-06-29 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | リハビリテーション / 脳卒中 / 運動 / エピジェネティクス / 運動療法 |
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| Outline of Final Research Achievements |
Repetitive administration of histone deacetylase (HDAC) inhibitor inhibited HDAC activity and acetylated histone H4 and H3 in the murine motor cortex, accompanying the increase of gene expression related to neuronal plasticity including neurotrophins and immediate-early genes. In the stroke model rats, acetylation level of histone H4 in the ipsilateral motor cortex decreased and HDAC activity in the ipsilateral hippocampus increased following stroke, whereas repetitive administration of HDAC inhibitor acetylated histone H4 in the motor cortex and inhibited HDAC activity in the hippocampus, suggesting that HDAC inhibition could recover the epigenetic condition in brain regions altered by stroke and beneficially present neuronal platform for stroke rehabilitation.
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| Academic Significance and Societal Importance of the Research Achievements |
脳卒中後の機能回復を目的とするリハビリテーションにおいて、運動療法は中枢神経系の可塑的変化を誘導し機能回復を促進する中心的な治療介入であるが、その効果を促進するための脳内環境のコンディショニングが期待される。本研究はヒストン脱アセチル化酵素（HDAC）阻害剤の投与による脳内エピジェネティクス環境の調整が可塑的遺伝子発現を増強すること、更に脳卒中によるエピジェネティクス変化を回復させる所見を得た。従って、エピジェネティクス制御が脳卒中リハビリテーション効果を増強するための有益な中枢性コンディショニングとなり得ることを示唆する基礎研究として本研究は学術的意義を有している。
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