Onset mechanism of Alzheimer's disease caused by diabetes focusing on alteration in cerebral insulin signaling
| Project/Area Number |
18K17954
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 59040:Nutrition science and health science-related
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| Research Institution | National Center for Geriatrics and Gerontology |
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Principal Investigator |
Tanokashira Daisuke 国立研究開発法人国立長寿医療研究センター, 統合加齢神経科学研究部, 外来研究員 (80724575)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 認知症 / アルツハイマー病 / 糖尿病 / 糖代謝調節経路 / インスリンシグナル |
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| Outline of Final Research Achievements |
We found that type 2 diabetes (DIO)-induced new Alzheimer's disease (AD) model (APPKI) mice (DIO-APPKI mice) were resistant to metabolic abnormalities induced by DIO, but their cognitive function tended to worsen compared to normal diet APPKI and DIO mice. Meanwhile, the reduction in hippocampal neurogenesis, which is associated with hippocampus-dependent cognitive function, was even more significantly reduced in these mice. Furthermore, changes in the modification of glucose metabolism signal component molecule, which were found in the postmortem brains of AD patients and increased in association with cognitive decline in DIO mice, were further enhanced in the hippocampus of these mice.
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| Academic Significance and Societal Importance of the Research Achievements |
2型糖尿病が認知症のリスク要因であることが広く知られるようになってきたが、認知機能と糖代謝経路のつながりを説明する詳細な分子機序については解明されておらず、適切なモデル動物系も確立されていなかった。次世代型ADモデルマウスに高脂肪食付加により2型糖尿病を誘導して作製したDIO-APPKIマウスは、世界ではまだ報告が無い新しいモデルマウスである。そのため、本モデルマウスの解析から得られた成果は、従来の認知症研究では見つからなかった新たな発見となり、認知症の新しい治療法や治療薬の開発に繋がることが期待される。
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Report
(4 results)
Research Products
(28 results)
