1998 Fiscal Year Final Research Report Summary
The investigation of relationship between genetic regulated mechanisms and epileptogenesis associated with epileptic brain
| Project/Area Number |
08671100
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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 |
Psychiatric science
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| Research Institution | Osaka City University |
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Principal Investigator |
YAMAGAMI Sakae Osaka City University, Medical School, Professor, 医学部, 教授 (20047004)
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| Co-Investigator(Kenkyū-buntansha) |
KATSUMOTO Eiichi Osaka City University, Medical School, Research Associate, 医学部, 助手 (90271189)
KIOKA Tetsurou Osaka City University, Medical School, Lecturer, 医学部, 講師 (40254396)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Epilepsy / EL mice / genetic expression / mRNA / hypoxia inducible factor 1alpha (HLF) / glial fibrially acidic protein (GFAP) / glutamate transporter-1 (GLT-1) / hippocampus CA1-3 |
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| Research Abstract |
1) HLF (hypoxia-inducible factor 1alpha-like factor) which was cloned by Ema et al.is induced by hypoxia as well as HIF alpha (hypoxia-inducible factor alpha).
EL mice have an inherited susceptibility to develop convulsions after they have been stimulated by being repeatedly tossed up once a week from age 4 weeks. No information is available regarding induction of HLF mRNA expression after seizures. We examined the induction and localization of HLF mRNA expression after seizures in EL mouse brain by RNase protection assay and in situ hybridization. The HLF mRNA expression was slightly induced during the interictal period, decreased immediately after seizures, and increased after 1.5 h ; triphagic peaks were observed at 6, 48, and 120 h. The HLF rnRNA during the interictal period was expressed intensively in CAl-3. dentate gyrus and piriform cortex and moderately in cerebral cortex and other brain regions.
2) The GFAP mRNA expression in EL mice after tossing-up-induced seizures showed a b
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iphasic pattern. The level increased for <less than or equal>4 h, peaked at 18 h, disappeared after 72 h, and increased again between 120 and 144 h. Subcutaneous injection of anisomycin before seizures produced the same pattern in GFAP mRNA expression, but to a lesser degree than that without anisomycin. Administration of anisomycin did not affect seizure susceptibility. The GFAP mRNA expression produced by bemegride-induced seizures in ddY mice was lower than that produced by tossing-up-induced seizures in EL mice. The expression of c-fos mRNA by seizures in anisomycin-pretreated EL mice was prolonged until 4 h after sei
3) GLT-1 mRNA expression induced a significant increase in the hippocampus and cerebral cortex of both seizure-susceptible EL[s] and seizure-nonexperienced EL[ns] mice compared with ddY mice. GLT-1 is considered to be a main factor maintaing low glutamate concentration. We proposed that EL mice show hyperactivity of glutamate synthesis and that a compensatory mechanism elevates GLT-1 mRNA expression in the hippocampis and cerebral cortex. Therefore, the findings showed that an increase of glutamate synthesis might cause epileptogenesis in El mice. Less
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