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

癫痫脑遗传调控机制与癫痫发生关系的研究

基本信息

批准号：
08671100
负责人：
YAMAGAMI Sakae
金额：
$ 1.47万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671100/
关键词：
Epilepsy EL mice genetic expression mRNA hypoxia inducible factor 1alpha (HLF)glial fibrially acidic protein (GFAP)glutamate transporter-1 (GLT-1)hippocampus CA1-3 グルタミン酸トランスポーター in situe hybridization GLT-1 GLAST EAACI glial

项目摘要

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

1)HLF（缺氧诱导因子1 α样因子）由Ema等al.is克隆，由缺氧诱导，以及HIF α（缺氧诱导因子α）JL小鼠具有遗传易感性，在从4周龄起每周一次反复投掷刺激后发生惊厥。没有关于癫痫发作后诱导HLF mRNA表达的信息。我们研究了诱导和定位的HLF mRNA表达的EL小鼠癫痫发作后的RNA酶保护试验和原位杂交。HLF mRNA的表达在发作间期有轻微的诱导，在发作后立即降低，1.5 h后升高，在6、48和120 h观察到三噬峰。发作间期HLF mRNA在CA 1 -3区表达较强。2）EL小鼠在投掷致痫后GFAP mRNA表达呈B型变化，在海马、齿状回、梨状皮质、大脑皮质和其他脑区呈中度表达 ...更多信息同相模式水平升高持续<less than or equal>4 h，在18 h达到峰值，72 h后消失，并在120 - 144 h之间再次升高。癫痫发作前皮下注射茴香霉素产生相同的模式GFAP mRNA的表达，但程度低于没有茴香霉素。茴香霉素的管理并没有影响癫痫发作的敏感性。在ddY小鼠中由美解眠诱导的癫痫发作产生的GFAP mRNA表达低于在EL小鼠中由投掷诱导的癫痫发作产生的GFAP mRNA表达。与ddY小鼠相比，茴香霉素预处理EL小鼠癫痫发作引起的c-fos mRNA表达延长至sei 3）GLT-1 mRNA表达诱导癫痫易感EL[s]和癫痫未经历EL[ns]小鼠海马和大脑皮层显著增加后4 h。GLT-1被认为是维持低谷氨酸浓度的主要因素。我们提出，EL小鼠表现出过度活跃的谷氨酸合成和补偿机制，提高GLT-1 mRNA的表达在海马和大脑皮层。因此，研究结果表明，谷氨酸合成的增加可能会导致癫痫发生在El小鼠。少