Harrison M B, Shumate M D, Lothman E W
Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Neuroscience. 1995 Apr;65(3):785-95. doi: 10.1016/0306-4522(94)00529-e.
Expression of the opioid peptides dynorphin and enkephalin is altered within the first 24 h after acutely induced seizures in certain experimental models of epilepsy. Using in situ hybridization, we examined the expression of prodynorphin and preproenkephalin messenger RNA acutely following induction of kindling with recurrent seizures and in two models of chronic temporal lobe epilepsy: (i) rats fully kindled with rapidly recurring hippocampal seizures; and (ii) rats surviving after self-sustaining limbic status epilepticus induced with focal electrical stimulation of the hippocampus. In naive animals, a ventral-dorsal gradient was identified in the expression of both prodynorphin and preproenkephalin messenger RNA in the dentate gyrus and expression of prodynorphin message was demonstrated for the first time in the ventral portion of cornu Ammonis regio superior. After stimulation producing rapidly recurring hippocampal seizures, acute decreases in prodynorphin messenger RNA were seen in the dentate gyrus and cornu Ammonis regio superior at 24 h after the last seizure. In contrast, increases in preproenkephalin messenger RNA expression were seen acutely in the dentate gyrus, with a decrease seen in the entorhinal cortex. The change in prodynorphin message expression in cornu Ammonis regio superior persisted in kindled animals that were studied after one month seizure-free period. There were no changes in preproenkephalin message in kindled animals studied after the one month seizure-free interval. No statistically significant changes were found for either prodynorphin or preproenkephalin message in the post-self-sustaining limbic status epilepticus group at one month following induced seizures. Acute changes in peptide expression may contribute to increased excitation in the dentate gyrus during induction of kindling, while the chronic change identified in cornu Ammonis regio superior may contribute directly to persistently increased excitability in this region.
在某些癫痫实验模型中，急性诱发癫痫发作后的最初24小时内，阿片肽强啡肽和脑啡肽的表达会发生改变。我们采用原位杂交技术，在反复癫痫发作诱导点燃后以及在两种慢性颞叶癫痫模型中，急性检测前强啡肽原和前脑啡肽原信使核糖核酸的表达：（i）因快速反复出现海马癫痫发作而完全点燃的大鼠；（ii）通过海马局灶性电刺激诱导产生自维持性边缘性癫痫持续状态后存活的大鼠。在未处理的动物中，在齿状回中发现前强啡肽原和前脑啡肽原信使核糖核酸的表达存在腹侧 - 背侧梯度，并且首次在海马结构上区腹侧部分证实了前强啡肽原信使核糖核酸的表达。在产生快速反复出现的海马癫痫发作的刺激后，在最后一次癫痫发作后24小时，齿状回和海马结构上区的前强啡肽原信使核糖核酸急性减少。相比之下，齿状回中前脑啡肽原信使核糖核酸表达急性增加，而内嗅皮质中则减少。在无癫痫发作一个月后研究的点燃动物中，海马结构上区前强啡肽原信使核糖核酸表达的变化持续存在。在无癫痫发作一个月间隔后研究的点燃动物中，前脑啡肽原信使核糖核酸没有变化。在诱发癫痫发作后一个月，自维持性边缘性癫痫持续状态组中，前强啡肽原或前脑啡肽原信使核糖核酸均未发现有统计学意义的变化。肽表达的急性变化可能有助于在点燃诱导期间齿状回兴奋性增加，而在海马结构上区发现的慢性变化可能直接导致该区域兴奋性持续增加。
