| Project/Area Number |
18K07456
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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 52010:General internal medicine-related
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| Research Institution | Juntendo University |
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Principal Investigator |
Yumiko Motoi 順天堂大学, 医学(系)研究科(研究院), 特任教授 (60338407)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | タウ蛋白 / アルツハイマー病 / プリオン様伝播 / 学習障害 / 伝播 / ストレイン / ミクログリア / 凝集 / プリオン |
|---|
| Outline of Final Research Achievements |
Human tauopathy brain injections into the mouse brain induce the development of tau aggregates; however, the features of this neurotoxicity remain unclear. One reason may be short observational periods because previous studies mostly used mutated-tau transgenic mice and needed to complete the study before these mice developed neurofibrillary tangles. To examine whether long-term incubation of Alzheimer’s disease (AD) brain in the mouse brain cause functional decline. We herein used Tg601 mice, which overexpress wild-type human tau, and non-transgenic littermates (NTg) and injected an insoluble fraction of the AD brain into the unilateral hippocampus. After a long-term (17-19 months) post-injection, mice exhibited learning deficits detected by the Barnes maze test, Aggregated tau pathology and increased Iba-I-positive microglia in the hippocampus. These results potentially implicate that long-term changes in non-mutated tau mice may reflect human pathological conditions.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、ヒトアルツハイマー病をマウス脳に注入することによりヒトアルツハイマー病類似の脳変化および症状を再現することを示すことができた。本マウスモデルをアルツハイマー病の薬剤探索に使用することができるであろう。
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