Romualdi P, Bregola G, Donatini A, Capobianco A, Simonato M
Department of Pharmacology, University of Bologna, Italy.
J Mol Neurosci. 1999 Aug-Oct;13(1-2):69-75. doi: 10.1385/JMN:13:1-2:69.
The opioid peptide dynorphin is thought to be implicated in specific types of seizures. In particular, complex partial seizures have been shown to cause release of dynorphin, activation of prodynorphin gene expression, and new peptide synthesis in the hippocampus. In this study, the kinetics of the seizure-induced changes in prodynorphin mRNA and ir-dynorphin A levels in the hippocampus have been compared with those induced in the temporal and frontal cortex, i.e., in other regions involved in the pathophysiology of complex partial seizures. Experiments have been run using kindling, one of the most valuable models of partial epilepsy. In the hippocampus (1) prodynorphin mRNA levels transiently increase (threefold) 1 h after kindled seizures, and return to baseline by 2 h, and (2) dynorphin A levels are slightly decreased at 1 h, but increase (twofold) at 2 h and return to baseline by 6 h. In the temporal and in the frontal cortex, a late (beginning at 2 h) and prolonged (up to 24 h) decrease in both prodynorphin mRNA and ir-dynorphin A levels have been observed. These data suggest that differential changes in dynorphin metabolism occur in different brain areas after seizures. The mechanisms and functional implications of this observation remain to be investigated.
阿片肽强啡肽被认为与特定类型的癫痫发作有关。特别是，复杂部分性发作已被证明会导致强啡肽释放、前强啡肽基因表达激活以及海马体中新肽的合成。在本研究中，将癫痫发作诱导的海马体中前强啡肽mRNA和免疫反应性强啡肽A水平的变化动力学与颞叶和额叶皮质（即参与复杂部分性发作病理生理学的其他区域）中诱导的变化动力学进行了比较。实验采用点燃模型进行，这是部分性癫痫最有价值的模型之一。在海马体中：（1）点燃性癫痫发作1小时后，前强啡肽mRNA水平短暂升高（三倍），并在2小时恢复至基线水平；（2）强啡肽A水平在1小时时略有下降，但在2小时时升高（两倍），并在6小时恢复至基线水平。在颞叶和额叶皮质中，观察到前强啡肽mRNA和免疫反应性强啡肽A水平均出现延迟（从2小时开始）且持续较长时间（长达24小时）的下降。这些数据表明，癫痫发作后不同脑区的强啡肽代谢发生了不同变化。这一观察结果的机制和功能意义仍有待研究。
