Knoblach S M, Kubek M J
Program in Medical Neurobiology, Indiana University School of Medicine, USA.
Neuroscience. 1997 Jan;76(1):85-95. doi: 10.1016/s0306-4522(96)00361-2.
Thyrotropin-releasing hormone and its receptor are differentially distributed throughout the limbic forebrain. In addition to its neuroendocrine function, several non-endocrine central nervous system effects of thyrotropin-releasing hormone and its analogs have been reported, including anticonvulsant effects in animals and humans. Kindling, as a model of temporal lobe epilepsy, produces elevations of endogenous thyrotropin-releasing hormone specifically in seizure-prone limbic regions. The present study used semi-quantitative in situ hybridization to characterize changes in thyrotropin-releasing hormone messenger RNA that occurred during the kindling process (partial kindling), as well as after fully kindled seizures. No significant change in thyrotropin-releasing hormone messenger RNA was detected 1 h postictally, whereas significant elevations were detected in the granule cell layer of the hippocampal dentate gyrus, diffuse nuclei of the amygdala and in layers II and III of piriform and entorhinal cortices from 3 to 48 h after a single generalized seizure in fully kindled rats. Peak messenger RNA expression occurred from 6 to 12 h postictally, with a decline at 24 h, followed by a precipitous return to undetectable levels by 48 h, except in the dentate gyrus. In marked contrast, partial kindling produced no detectable change in thyrotropin-releasing hormone messenger RNA by 6 h after the first occurrence of stage 1-5 seizures. Electrode placement, a single afterdischarge, or a 20-microA stimulation of the amygdala was not associated with accumulation of thyrotropin-releasing hormone messenger RNA. Thus, only full kindled generalized seizures increased thyrotropin-releasing hormone messenger RNA expression in identical limbic regions which also showed postictal elevations in thyrotropin-releasing hormone. However, this enhancement followed a more immediate and shorter lasting time-course than previously demonstrated increases in the tripeptide. These results support the hypothesis that thyrotropin-releasing hormone is an important neuromodulator in epileptic foci.
促甲状腺激素释放激素及其受体在边缘前脑呈差异性分布。除了其神经内分泌功能外，促甲状腺激素释放激素及其类似物还具有多种非内分泌中枢神经系统效应，包括在动物和人类中的抗惊厥作用。点燃作为颞叶癫痫的一种模型，会使内源性促甲状腺激素释放激素在易发作的边缘区域特异性升高。本研究采用半定量原位杂交技术，以表征在点燃过程（部分点燃）以及完全点燃发作后促甲状腺激素释放激素信使核糖核酸（mRNA）的变化。在发作后1小时未检测到促甲状腺激素释放激素mRNA的显著变化，而在完全点燃的大鼠单次全身性发作后3至48小时，在海马齿状回的颗粒细胞层、杏仁核的弥散核以及梨状皮质和内嗅皮质的II层和III层中检测到显著升高。mRNA表达峰值出现在发作后6至12小时，24小时时下降，到48小时时急剧降至检测不到的水平，但在齿状回除外。与之形成鲜明对比的是，在首次出现1 - 5期发作后6小时，部分点燃未导致促甲状腺激素释放激素mRNA出现可检测到的变化。电极放置、单次放电后发放或20微安的杏仁核刺激均与促甲状腺激素释放激素mRNA的积累无关。因此，只有完全点燃的全身性发作会增加相同边缘区域促甲状腺激素释放激素mRNA的表达，这些区域在发作后促甲状腺激素释放激素也会升高。然而，这种增强作用的时间进程比先前证明的三肽增加更为迅速且持续时间更短。这些结果支持了促甲状腺激素释放激素是癫痫病灶中重要神经调节剂的假说。
