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

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)采用0.02%丙硫脲嘧啶（PTU）在新生儿乳中暴露的方法，建立了致听性癫痫易感大鼠。c-fos mRNA原位杂交显示，ptuv治疗大鼠的听原性癫痫发作始于脑干，尤其是下丘，而非海马。这也表明NMDA受体在下丘中起主要作用。2)相比之下，基因癫痫易感大鼠如自发性癫痫大鼠（SER）和Ihara的基因癫痫大鼠（IGER），如先前报道的，表现为边缘癫痫发作，主要涉及海马。在这两种遗传模型中，我们发现海马中神经肽Y （NPY）含量显著升高。3)建立三甲基锡（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，在tmt治疗的大鼠中，内分泌和免疫参数如皮质酮和细胞因子的变化被发现先于神经肽的变化。

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.