Vernier P, Julien J F, Rataboul P, Fourrier O, Feuerstein C, Mallet J
Département de Génétique Moléculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
J Neurochem. 1988 Nov;51(5):1375-80. doi: 10.1111/j.1471-4159.1988.tb01100.x.
The time course changes in levels of mRNA encoding glutamic acid decarboxylase (GAD) and proenkephalin (PPE) was analyzed in the rat striatum following unilateral lesion of substantia nigra with 6-hydroxydopamine. The levels of both GAD and PPE mRNAs increased after the dopaminergic deafferentation, reaching concomitantly a maximal twofold increase on day 25. Thereafter, the mRNA levels declined; at 4 months, the amount of PPE mRNA remained slightly elevated whereas GAD mRNA had returned to the control value, suggesting the action of a compensatory mechanism. We also observed a rise of glial fibrillary acidic protein mRNA level which reflects a reactive astrocytosis. In contrast, alpha-tubulin mRNA level remained unchanged, indicating that no significant synaptogenesis occurs in this experimental situation. No obvious modification in mRNA levels was detected in the striatum contralateral to the lesion. These results highlight the role of the modulation of gene expression in adaptive processes to dopamine deficiency in striatal efferent pathways. Its relevance to the pathophysiology of Parkinson's disease is discussed.
在用6-羟基多巴胺单侧损伤黑质后，分析了大鼠纹状体中编码谷氨酸脱羧酶（GAD）和前脑啡肽（PPE）的mRNA水平的时程变化。多巴胺能去传入后，GAD和PPE mRNA水平均升高，在第25天同时达到最大两倍的增加。此后，mRNA水平下降；在4个月时，PPE mRNA量仍略有升高，而GAD mRNA已恢复到对照值，提示存在一种代偿机制的作用。我们还观察到反映反应性星形细胞增多的胶质纤维酸性蛋白mRNA水平升高。相反，α-微管蛋白mRNA水平保持不变，表明在这种实验情况下没有明显的突触发生。在损伤对侧的纹状体中未检测到mRNA水平的明显改变。这些结果突出了基因表达调节在纹状体传出通路对多巴胺缺乏的适应性过程中的作用。讨论了其与帕金森病病理生理学的相关性。
