| Project/Area Number |
21K17565
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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) |
2021-04-01 – 2022-03-31
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| Project Status |
Discontinued (Fiscal Year 2021)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | light-intensity exercise / astaxanthin / leptin / Alzheimer’s disease / amyloid β / neurogenesis / spatial memory / Alzheimer's disease / Exercise / Astaxanthin / Neuroplasticity / Leptin |
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| Outline of Research at the Start |
This study is to investigate the brain mechanism underlying neuroplastic benefit by a combined strategy with light exercise and astaxanthin supplementation in the mouse model of Alzheimer's disease. The prospective findings could be used as a scientific basis to develop practical applications.
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| Outline of Annual Research Achievements |
Using the Alzheimer’s disease (AD) model (APPNL-G-F mice) developed by the RIKEN, which demonstrates pathological phenotypes of human patients with AD, we aimed to investigate whether a long-term combined intervention of light-intensity exercise (LE) and astaxanthin (ASX) intake facilitate the hippocampal-dependent neural plasticity and subsequent cognitive enhancement in AD, thereby elucidating the role of brain-genic leptin (LEP) as a potential molecule target. We investigated pathological phenotypes and LEP expression shown in age-matched wild-type mice as a control, APPNL-G-F and APPNL-G-F treated with LE, and APPNL-G-F mice combined-treated with LE and ASX. It revealed that the pathological phenotypes featured by the impaired spatial memory in Morris water maze test and the accumulation of amyloid β-peptide as well as the overexpression of LEP in the hippocampus, might be reversed by combined treatment of LE and ASX. Furthermore, we found the synergistic improvement in the hippocampal neurogenesis and BDNF expression by combined treatment of LE and ASX of APPNL-G-F mice. However, we are still confronting the growing debates about whether the source of LEP detected in the brain is actually the brain. To reveal the origin of LEP, we established an in situ hybridization technique, and as of now, we have made great progress on this and tentatively succeeded in labeling LEP mRNA in hippocampal CA2/3 region. There is a lot to unravel, but these findings will give a new insight into hippocampal neuroplasticity mediated by LEP in patients with AD.
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