The investigation of relationship between genetic regulated mechanisms and epileptogenesis associated with epileptic brain

1)EMA等人克隆的HLF(低氧诱导因子1α)与HIFα(低氧诱导因子α)一样受低氧诱导。EL小鼠从4周龄开始每周反复抛起一次刺激，具有发生惊厥的遗传易感性。目前还没有关于癫痫发作后诱导HLF基因表达的信息。采用核糖核酸酶保护法和原位杂交技术检测癫痫发作后EL小鼠脑组织HLF基因表达的变化。发作间期HLF mRNA表达水平较低，癫痫发作后即刻表达下降，1.5 h后表达增强，6、48、120 h出现三重峰，发作间期HLF rnRNA在CAL-3中表达较强。海马齿状回和梨状皮质，在大脑皮层和其他脑区有中等程度的表达。2)翻转致痫小鼠癫痫发作后GFAP mRNA的表达呈b…更多的是间歇性模式。癫痫发作前皮下注射茴香霉素组GFAP基因表达水平与对照组相同，但幅度较小。给予茴香霉素并不影响癫痫的敏感性。Ddy小鼠由美解眠诱导的癫痫发作产生的GFAP mRNA表达低于EL小鼠由翻腾致痫产生的GFAP mRNA表达。(3)与ddy小鼠相比，癫痫易感组[S]和无发作组[ns]小鼠海马区和大脑皮层中GLT-1mRNA表达均显著增加。GLT-1被认为是维持低谷氨酸浓度的主要因素。我们认为，EL小鼠表现出谷氨酸合成的过度活跃，并且一种代偿机制提高了海马区和大脑皮层GLT-1mRNA的表达。因此，研究结果表明，谷氨酸合成增加可能导致EL小鼠癫痫的发生。较少

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 … More 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 sei3) 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