| Project/Area Number |
11672195
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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 |
Biological pharmacy
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| Research Institution | Hokuriku University |
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Principal Investigator |
TAKADERA Tsuneo Hokuriku University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (90121277)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | NMDA receptor / calcium ion / apoptosis / caspase / MK-801 / ifenprodil / ethanol / 大脳皮質細胞 / カスパーゼ3 |
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| Research Abstract |
The NMDA receptor and receptor-associated ion channel are assumed to play a principal role in glutamate excitotoxicity on neurons of the cortex and hippocampus. NMDA antagonists (NK801, APV) and ethanol inhibit the NMDA neurotoxicity in cultured cortical neurons. However, NMDA antagonists and ethanol are known to be toxic to certain neuronal populations. In the present study, we have examined whether NMDA antagonists and ethanol induce neuronal apoptosis in a culture condition. Exposure of rat cortical cultures (10 days in vitro) to MK801 (1 nM to 10 μM ) and ethanol (50 to 300 mM) for 24 to 48 hr resulted in apoptotic cell death in a dose-dependent manner. NMDA (25 and 50 μM) attenuated the MK801-and ethanol-induced cell death. MK801 and ethanol decreased intracellular calcium ion concentrations. Activation of caspase-3 was accompanied by MK801-and ethanol-induced cell death in a dose-dependent manner. Further, cycloheximide (0.1 and 0.2 μg/ml) protected the cells from MK801 and ethanol-induced cell death and caspase-3 activation. Insulin-like growth factor 1 (5 to 20 ng/ml) also inhibited the cell death and caspase-3 activation induced by MK801 and ethanol. Ifenprodil, a NR2B-selective NMDA antagonist, also induced apoptotic cell death and caspase-3 activation. These results indicate that the moderate NMDA receptor activation may support the survival of neurons during the neuronal development, and drugs which inhibit NMDA receptor may induce apoptosis.
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