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Molecular biological study on the mechanisms underlying seizure susceptibility and seizure development

癫痫易感性和癫痫发展机制的分子生物学研究

基本信息

批准号：
08671084
负责人：
KATO Nobumasa
金额：
$ 1.54万
依托单位：
Shiga University of Medical Science
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 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671084/
关键词：
epilepsy immediate early gene hippocampus inferior colliculus glutamate receptors neuropeptide Y ニューロペプチド Y c-fos in situ hybridization ラット

项目摘要

The present study was conducted to investigate neural mechanisms underlying geizure susceptibility and development with use of experimental models of epilepsy. The results were as follows : 1)Audiogenic seizure-prone rats were established by means of neonatal exposure to 0.02% propylthiouracil (PTU) through mother's milk. In situ hybridization of c-fos mRNA revealed that audiogenic seizure in these PTU-treated rats initiated in the brainstem, especially in inferior colliculus and not hippocampus. It is also suggested that NMDA receptors play a primary role within inferior colliculus.2)In contrast, genetically epilepsy-prone rats such as spontaneously epileptic rats (SER) and Ihara's genetically epileptic rats (IGER), exhibit linmbic seizures, in which hippocampus is primarily involved as reported previously. In these two genetic models we found the significant elevation of neuropeptide Y (NPY) contents in the hippocampus.3)Then, we adopted a model of selective damage in the hippocampus following trimethyltin (TMT) intoxication in the rats. In these TMT-treated rats, expression of NPY mRNA was found to be elevated in the hippocampus. Furthermore, changes in endocrine and immunological parameters such as corticosterone and cytokines were found to precede those in neuropeptides in TMT-treated rats.

本研究利用癫痫实验模型探讨癫痫易感性和发展的神经机制。结果如下：（1）通过母乳给予新生大鼠0.02%丙基硫氧嘧啶（PTU），建立听源性惊厥易感大鼠模型。c-fos mRNA的原位杂交结果显示PTU处理组大鼠的听源性癫痫发作起始于脑干，尤其是下丘，而非海马。2）与此相反，遗传性癫痫易感大鼠如自发性癫痫大鼠（SER）和Ihara遗传性癫痫大鼠（IGER）表现出边缘性癫痫发作，海马主要参与其中。在这两种遗传模型中，均发现海马神经肽Y（neuropeptide Y，NPY）含量显著升高。3）采用三甲基锡（trimethyltin，TMT）中毒大鼠海马选择性损伤模型。在这些TMT治疗的大鼠中，发现海马中NPY mRNA的表达升高。此外，内分泌和免疫参数，如皮质酮和细胞因子的变化被发现之前，在TMT治疗大鼠的神经肽。