| Project/Area Number |
25640031
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
IHARA Masafumi 独立行政法人国立循環器病研究センター, 病院, 医長 (00372590)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 長寿遺伝子 / サーチュイン / SIRT1 / 血管性認知症 / 脳梗塞 / 脳卒中 / 内皮型一酸化窒素合成酵素 / 血液脳関門 / Sirt1 / 両側総頸動脈狭窄術 / 一酸化窒素 / 脳循環予備能 / レスベラトロール |
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| Outline of Final Research Achievements |
SIRT1 belongs to the sirtuin family of protein deacetylases which mediate extensions of lifespan and suppress cerebrovascular diseases in model organisms. We hypothesized that neurovascular protection incorporates the broad-range effects of SIRT1. To test this, we generated Sirt1-overexpressing (Sirt1-Tg) mice driven by a prion promoter to determine whether Sirt1-Tg mice protect consequences of cerebral hypoperfusion in vivo. Cerebral hypoperfusion induced by bilateral common carotid artery stenosis caused memory impairment and histological changes in wild-type mice. However, these phenotypes were rescued in Sirt1-Tg mice, where cerebral blood flow was maintained even poststenosis. Brain endothelial nitric oxide synthase was acetylated after cerebral hypoperfusion in wild-type littermates but remained unacetylated in Sirt1-Tg mice. Our results indicate that neurovascular endothelial SIRT1 potentiation upregulates the nitric oxide system and counters cerebral hypoperfusion injury.
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