| Project/Area Number |
25250010
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
SAITOE Minoru 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 基盤技術研究センター長 (50261839)
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| Co-Investigator(Renkei-kenkyūsha) |
MIYASHITA Tomoyuki 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 主席研究員 (70270668)
UENO Kohei 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 副参事研究員 (40332556)
MATSUNO Motomi 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 主席研究員 (90392365)
HIRANO Yukinori 京都大学, 医学研究科メディカルイノベーションセンター, 准教授 (40580121)
NAGANOS Shintaro 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 主任研究員 (30631965)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥34,710,000 (Direct Cost: ¥26,700,000、Indirect Cost: ¥8,010,000)
Fiscal Year 2015: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2014: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2013: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
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| Keywords | 老化 / 記憶 / ショウジョウバエ / D-セリン / 脳神経 / 学習記憶 / グリア / 脳・神経科学 |
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| Outline of Final Research Achievements |
Age-related memory impairment (AMI) is a debilitating consequence of brain aging that can be suppressed in Drosophila by reducing PKA activity. However, the molecular mechanisms underlying AMI remain unclear. In the previous study, we found that age-associated increase in the activity of Drosophila pyruvate carboxylase (dPC), a mitochondrial anaplerotic enzyme, causes AMI. In this study, we clarify that dPC functions downstream of DC0-PK; DC0 mutations decrease expression of dPC and AMI in DC0 mutants is restored by expressing dPC in the glial cells whereas memory defects caused by overexpression of DC0 is suppressed by dPC mutations. Given that dPC activity suppresses serine racemase, enzyme that convert L-serine to D-serine, D-serine level was decreased upon aging in the wild type brain, while it was not altered in dPC/+ brain. Similarly, D-serine level was not changed upon aging in DC0/+ brain. Remarkably, AMI was significantly improved in wild-type by fed them with D-serine.
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