| Project/Area Number |
23650198
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | 公益財団法人東京都医学総合研究所 (2012)
Tokyo Metropolitan Organization for Medical Research (2011) |
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Principal Investigator |
SAITOE Minoru 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 参事研究員 (50261839)
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| Co-Investigator(Kenkyū-buntansha) |
HORIUCHI Junjiro 首都大学東京, 理工学研究科, 准教授 (80392364)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 老化 / 学習記憶 / ショウジョウバエ / ピルビン酸カルボキシラーゼ / D-セリン / (1)学習記憶 / (2)老化 / (3)グリア / (4)乳酸 / (5)ショウジョウバエ |
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| Research Abstract |
Age-related memory impairment (AMI) is a debilitating consequence of brain aging and caused by age-related increase in pyruvate carboxylase (PC), a mitochondrial anaplerotic enzyme, in Drosophila. As increase in PC may suppress synthesis of lactate, glia-derived energy source for neurons, in this study, we tried to demonstrate that increase in PC activity inhibits glia-neuron lactate shuttle (GNLS) thereby impairs memory formation. However, our behavioral and biochemical data demonstrated that PC-dependent memory defects are not caused by GNLS inhibition. Although increase in PC activity does not inhibit GNLS, it may inhibit serine racemase (SR) via increasing biosynthesis of its potent inhibitors oxaloacetate (OAA) and aspartate (Asp). SR converts L-serine to D-serine, a glia-derived NMDA receptor agonist. As we expected, D-serine/L-serine ratio is significantly decreased in aged AMI-suffered flies, and this decrease is suppressed by dPC mutations. Furthermore, both AMI and memory defects caused by overexpressing PC in glia are ameliorated by feeding flies D-serine. We propose that age-related increases in glial mitochondrial dPC activity cause AMI by reducing D-serine production.
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