| Project/Area Number |
12680802
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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 |
神経・脳内生理学
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| Research Institution | Kurume University School of Medicine |
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Principal Investigator |
YAMAMOTO Satoshi Kurume Univ. Sch. Med., Physiol., Research Assistante, 医学部, 助手 (60220464)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Eiichiro Kurume Univ. Sch. Med., Physiol., Assistant Professor, 医学部, 講師 (80188284)
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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 |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Apoptosis / Necrosis / Brain ischemia / Hippocampal CA1 pyramidal neuron / 海馬CA1細胞 |
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| Research Abstract |
Purpose : Study of cross talk between apoptosis and necrosis in the ischemic neuronal cell death.
Method : (1) Enzymatic activities of apoptosis-inducing protein, caspase3 in the ischemic necrosis model and (2) the effect of the apoptosis-suppressing protein, such as heat shock proteins for the necrosis model were examined in the hippocampal pyramidal neurons of the rat.
Results : (1) The membrane of the CAl pyramidal neuron rapidly depolarized 6min after in vitro ischemia (rapid depolarization : RD) and the depolarization persisted even when the ischemia was teminated. At this point balloon-shaped neurons were observed, showing neuronal necrosis. In this necrosis model, the enzymatic activity of caspase3 was increased according as exposure time of the ischemia was prolonged. (2) Intra-peritoneum administration of low dose of kainic acid (KA)(5mg/kg) to the rat induces heat shock proteins in CAl area of the hippocampus, and apoptosis of CAl neuron caused by in vivo ischemia can be reduced by pretreatment of KA. By the pretreatment, the RD produced by in vitro ischemia was significantly prolonged and the number of neurons that the membrane potential was restored to the pre-ischemic level was increased. These effects were maximal at 3 days after the treatment and the effect for the RD could be inhibited by protein synthesis inhibitor, cycloheximide. There were no significant differences in electrical membrane properties of CAl neuron, release efficiency of glutamate from nerve terminals and glutamate receptor sensitivity between non-treated and treated rats. the slow DC potential that was activated by termination of ischemi was increased in KA-pretreated rats.
Conclusion : Activation of apoptosis-inducing protein in necrosis model and inhibition of both necrosis and apoptosis by pretreatment of KA suggest the possibility of existence of cross talk between apoptosis and necrosis.
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