| Project/Area Number |
12680756
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | KYOTO UNIVERSITY (2001)
Ehime University (2000) |
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Principal Investigator |
MITANI Akira Kyoto University, College of Medical Technology, Professor, 医療技術短期大学部, 教授 (50200043)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Kohichi Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (80171750)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | glutamate neurotoxicity / ischemia / transporter / glia / hippocampus / microdialysis / KO mouse / GLT-1 / グルタミン酸毒性 / GLT-1ノックアウトマウス |
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| Research Abstract |
The glutamate transport is the only mechanism for removal of glutamate from the extracellular fluid in the brain, therefore, dysfunction or functional changes in glutamate transporters may be involved in the process of increase in extracellular glutamate during ischemia. In the present study, we performed in vivo brain microdialysis experiments in the mice genetically lacking GLT-1, and examined the role of GLT-1 in increase in the extracellular glutamate during ischemia. A microdialysis probe was placed in the hippocampal CA1 of wild type mice and mice lacking GLT-1, and glutamate levels were measured during 5- and 20-min ischemia. Histological examinations were also performed. The glutamate levels during 5-min ischemia in mice lacking GLT-1 were significantly higher than the corresponding glutamate levels in wild type mice. Delayed neuronal death following 5-min ischemia was induced in the CA1 of the mice lacking GLT-1 but not in the CA1 of the wild type mice. The glutamate levels during the last 12.5 minutes of 20-min ischemia in wild type mice were significantly higher than the corresponding glutamate levels in mice lacking GLT-1. Acute neuronal death was induced in the CA1 of mice lacking GLT-1 and also in the CA1 of the wild type mice. These results suggest that GLT-1 changes in function during ischemia : It removes extracellular glutamate to protect neurons during 5-min ischemia and releases glutamate, triggering acute neuronal death, during the last 12.5 minutes of 20-min ischemia.
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