Project/Area Number |
25670155
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
General medical chemistry
|
Research Institution | 独立行政法人医薬基盤研究所 |
Principal Investigator |
TAKEMORI Hiroshi 独立行政法人医薬基盤研究所, 創薬基盤研究部, プロジェクトリーダー (90273672)
|
Project Period (FY) |
2013-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | Grid2 / BDNF / 運動記憶 / 遺伝学 / マイクロサテライト解析 / GRID2 / メマンチン / NMDA / AMPA / めまい |
Outline of Final Research Achievements |
We identified a mouse strain with a naturally occurring mutation and an ataxic phenotype that presents with severe leg cramps. To investigate the phenotypes of these mutant mice, we screened several phenotype-modulating drugs and found that memantine (10 mg/kg) disrupted the sense of balance in the mutants. Moreover, the mutant mice showed an attenuated optokinetic response (OKR) and impaired OKR learning, which was also observed in wild-type mice treated with memantine. Microsatellite analyses indicated that the Grid2 gene-deletion is responsible for these phenotypes. Patch-clamp analysis showed a relatively small change in NMDA-dependent current in cultured granule cells from Grid2 gene-deleted mice, suggesting that GRID2 is important for correct NMDA receptor function.In addition, Grid2 mutant mice expressed abnormal BDNF protein, suggesting tat Grid2 mutant mice is helpful to analyze NMDA-R related memory.
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