| Project/Area Number |
18K17790
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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 59020:Sports sciences-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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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 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 低強度運動 / 海馬 / グルタミン酸 / アルツハイマー病 / ストレス / 神経新生 / 認知機能 |
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| Outline of Final Research Achievements |
Using Alzheimer's disease model animals (5XFAD), we examined the hypothesis that abnormal glutamate metabolism is responsible for amyloid β accumulation and cognitive decline. In the experiment, riluzole, which activates the glutamate transporter and promotes the uptake of glutamate into astrocytes, was administrated for 6 months. As a result, it was clarified that long-term administration of riluzole suppressed that the accumulation of amyloid β in the subiculum and frontal cortex and improved the cognitive decline observed in 5XFAD mice. In addition, as a result of comprehensive analysis of gene expression by RNA-Seq, it was found that abnormalities in gene expression in the hippocampus associated with Alzheimer's disease, especially associated microglia, were also improved by administration of riluzole.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果はアルツハイマー病に伴うアミロイドβの蓄積や認知機能の低下は、細胞外に過剰に放出されたグルタミン酸が要因であり、海馬のグルタミン代謝の恒常性を保つことが、海馬をストレスに伴う疾患から守る上で重要であることを示唆するものである。一過性の低強度運動により海馬のグルタミン酸濃度が上昇する傾向を示しており、習慣的な運動による適度なグルタミン酸放出の繰り返しが、グルタミン酸の恒常性（放出されたグルタミン酸の取り込み・除去など）を強化し、ストレス適応力を高めていることが想定される。これらの知見は、運動がストレスに打ち克つための脳を育む分子機構を解明する糸口となることが期待される。
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