| Project/Area Number |
15390436
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kyoto University |
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Principal Investigator |
MITANI Akira Kyoto University, Faculty of Medicine, Professor, 医学部, 教授 (50200043)
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| Co-Investigator(Kenkyū-buntansha) |
NOMURA Sakashi Kyoto University, Faculty of Medicine, Professor, 医学部, 教授 (60034188)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | glutamate / transporter / ischemia / hippocampus / microdialysis / 脳虚血性ニューロン死 / ノックアウトマウス |
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| Research Abstract |
Glutamate transporters remove glutamate from the extracellular space and maintain it below neurotoxic levels under normal conditions. However, the dynamics under ischemic conditions remain to be determined. In the present study, we evaluated the function of the glial glutamate transporter (GLT-1) and neuronal glutamate transporter (EAAC1) during brain ischemia, by using an in vivo brain microdialysis technique in the mutant mice. A microdialysis probe was placed in the hippocampal CA1 of the mutant and wild-type mice, and glutamate levels were measured during 5- and 20-min ischemia. The glutamate levels in mice lacking GLT-1 were significantly higher than the corresponding glutamate levels in wild-type mice during 5-min ischemia. Delayed neuronal death was induced in the CA1 of the mice lacking GLT-1 but not in the CA1 of the wild-type mice. When ischemia was elongated to the duration of 20 min, the glutamate levels in wild-type mice were significantly higher than the corresponding glutamate levels in mice lacking GLT-1 during the last 12.5 min of 20-min ischemia. Acute neuronal death was also observed in the CA1 of the wild-type mice. These results suggest that GLT-1 takes up extracellular glutamate to protect neurons in early stage of ischemia and then releases glutamate, triggering acute neuronal death, when ischemic conditions are elongated. The function of GLT-1 may change from neuroprotective to neurodegenerative during ischemia. The glutamate levels in mice lacking EAAC1 were significantly lower than the corresponding glutamate levels in wild-type mice during ischemia. This result suggests that EAAC1 releases glutamate immediately after ischemia. EAAC1 may act neurodegeneratively from the early stage of ischemia.
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