2021 Fiscal Year Final Research Report
Analysis of the mechanism of effects of habitual exercise on cognitive dysfunction induced by amyloid beta oligomers
| Project/Area Number |
19K11362
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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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| Review Section |
Basic Section 59010:Rehabilitation science-related
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| Research Institution | National Institute of Advanced Industrial Science and Technology |
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Principal Investigator |
OCHIISHI TOMOYO 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (30356729)
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| Co-Investigator(Kenkyū-buntansha) |
清末 和之 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ長 (50356903)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | アルツハイマー病 / アミロイドβタンパク質 / トランスジェニックマウス / オリゴマー / シナプス / 運動 / 認知機能 |
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| Outline of Final Research Achievements |
It is well known that habitual exercise improves cognitive function in the elderly. Therefore, habitual exercise is attracting attention as a part of prevention against the onset of AD or as a new therapeutic intervention. However, the mechanism by which habitual exercise can improve the efficiency of synaptic transmission is unknown. Recently it suggested that oligomers of intracellular amyloid β (Aβ) are strongly cytotoxic, and play crucial roles in the cognitive function in AD. To investigate the effects of the voluntary exercise loading in early stage of AD, we used Aβ-GFP transgenic mouse that express fusion protein of Aβ and GFP that consisting of Aβ oligomers inside neurons. After 2 months of voluntary exercise loading to this mouse with a running wheel, the memory deficits were significantly improved. In addition, a comprehensive DNA microarray analysis of genes whose expression fluctuated before and after exercise revealed changes in synaptic-related proteins.
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| Free Research Field |
神経細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
Aβオリゴマーを神経細胞内にのみ発現するAβ-GFPマウスは重篤なアルツハイマー病（AD）の病理学的所見を示さないが、生後２-３ヶ月齢で認知機能が低下することから軽度認知障害(MCI)のモデルとして使用できる。このモデルマウスを用いた習慣的な運動による、認知機能改善効果の解析系はMCIや発症初期のAD患者において運動の効果のメカニズムについて新たな知見をもたらすことが可能である。また、AD治療の非薬物的介入のみでなく、運動による効果を高める物質等、薬物的治療法の開発にも繋がることが期待される。高齢化社会において、医療費や介護の問題などの社会問題解決に向けて、発症予防という観点からも意義がある
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