| Project/Area Number |
15K12570
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Rehabilitation science/Welfare engineering
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
齊藤 展士 北海道大学, 保健科学研究院, 助教 (60301917)
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| Research Collaborator |
Kanemura Naohiko
Kokubun Takanori
Murata Kenji
Takayanagi Kiyomi
Inoue Takahiro
Okuda Akane
Ninuma Shuta
Hayashi Masataka
Takahashi Kazuma
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 神経栄養因子 / 運動 / 老化 / 海馬 / 認知機能 / エピジェネティクス |
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| Outline of Final Research Achievements |
The objective of the present study was to assess the interactive effects of exercise and aging on cognitive function, expression of neurotrophins (BDNF and neurotrophin-4) and their receptors (tyrosine receptor kinase B and p75), and epigenetic regulations, including the activity of HATs and HADCs in the hippocampus. We used the senescence-accelerated mouse resistant 1(SAMR1) and prone 1 (SAMP1) lines. Mice in the exercise groups exercised on a treadmill. Exercise for 4 weeks improved cognitive function, accompanied by an increase in BDNF expression and a decrease in p75 transcription in both SAMR1 and SAMP1. The exercise regimen activated both HAT and HDAC in the hippocampus. Therefore, the present study reveals that despite accelerated senescence, long-term exercise improved cognitive function, upregulated the expression of BDNF, and downregulated p75, a receptor involved in apoptotic signaling, accompanying the modulation epigenetic markers.
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| Academic Significance and Societal Importance of the Research Achievements |
高齢者を対象とする運動療法は、運動機能のみならず認知症をはじめとする中枢神経系の退行に対して、幅広くその進行を抑制し、予防効果を有することが注目されている。老齢モデルマウスを対象に運動介入による脳におけるシナプス受容体、脳由来神経因子等の遺伝子発現とそれを制御する酵素活性について検証することにより、運動療法に伴う脳における可塑的遺伝子発現の修飾に関わる機構の解明を試みた。
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