Gerfen C R, McGinty J F, Young W S
Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland 20892.
J Neurosci. 1991 Apr;11(4):1016-31. doi: 10.1523/JNEUROSCI.11-04-01016.1991.
Dopamine regulation of the levels of dynorphin, enkephalin, and substance P messenger RNAs in rat striatal neurons was analyzed with in situ hybridization histochemistry (ISHH). Relative levels of peptide mRNA expression in the patch and matrix compartments of the dorsolateral striatum were compared among control rats, rats treated for 10 d with apomorphine, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic system, and rats with nigrostriatal dopaminergic lesions followed 2 weeks later by 10 d of apomorphine treatment. Image analysis of ISHH labeling demonstrated that the number of neurons expressing each peptide mRNA remained constant, whereas the relative level of peptide mRNA per neuron changed significantly, depending on the experimental treatment. Dynorphin mRNA expression increased following chronic apomorphine treatment: striatal patch neurons increased to an average of 100% above control values, whereas striatal matrix neurons showed only a 25% increase. Dynorphin mRNA expression decreased following 6-OHDA lesions: patch neurons showed an average 75% reduction in expression, whereas matrix neurons showed no significant change. In animals with 6-OHDA lesions followed by apomorphine treatment, both patch and matrix neurons showed an average increase in dynorphin expression of 300% above control levels. Changes in dynorphin mRNA levels with these treatments were matched by qualitative changes in dynorphin immunoreactivity both in the striatum and in striatonigral terminals in the substantia nigra. Neither substance P nor enkephalin mRNA levels showed a significant difference between the striatal patch and matrix compartments in any experimental condition (in the dorsolateral striatum). Substance P mRNA expression was increased an average of 50% after 10 d of apomorphine treatment and showed an average decrease of 75% following 6-OHDA lesions of the mesostriatal system. There was no significant change in the expression of substance P mRNA in striatal neurons compared to control values in rats with combined 6-OHDA lesion and apomorphine treatment. Enkephalin mRNA expression was not significantly altered by chronic apomorphine treatment but showed an average increase per cell of some 130% above control levels following 6-OHDA-induced lesions of the mesostriatal system. In animals with a 6-OHDA lesion and apomorphine treatment, enkephalin mRNA was also elevated but not significantly above the levels produced by the lesions alone. These data show that the expression of dynorphin, enkephalin, and substance P is differentially regulated by the mesostriatal dopaminergic system and, further, suggests that the mechanisms by which this regulation occurs may be different for the 3 peptide families.
采用原位杂交组织化学（ISHH）技术分析了多巴胺对大鼠纹状体神经元中强啡肽、脑啡肽和P物质信使核糖核酸（mRNA）水平的调节作用。比较了对照组大鼠、用阿扑吗啡处理10天的大鼠、黑质纹状体多巴胺能系统单侧6-羟基多巴胺（6-OHDA）损伤的大鼠以及黑质纹状体多巴胺能损伤后2周再用阿扑吗啡处理10天的大鼠背外侧纹状体中斑块和基质区室中肽mRNA表达的相对水平。ISHH标记的图像分析表明，表达每种肽mRNA的神经元数量保持不变，而每个神经元中肽mRNA的相对水平根据实验处理而有显著变化。慢性阿扑吗啡处理后强啡肽mRNA表达增加：纹状体斑块神经元增加至比对照值平均高出100%，而纹状体基质神经元仅增加25%。6-OHDA损伤后强啡肽mRNA表达降低：斑块神经元表达平均降低75%，而基质神经元无显著变化。在6-OHDA损伤后再用阿扑吗啡处理的动物中，斑块和基质神经元中强啡肽表达均比对照水平平均增加300%。这些处理导致的强啡肽mRNA水平变化与纹状体和黑质中纹状体黑质终末的强啡肽免疫反应性的定性变化相匹配。在任何实验条件下（背外侧纹状体中），P物质和脑啡肽mRNA水平在纹状体斑块和基质区室之间均无显著差异。阿扑吗啡处理10天后，P物质mRNA表达平均增加50%，而中脑纹状体系统6-OHDA损伤后平均降低75%。与6-OHDA损伤合并阿扑吗啡处理的大鼠的对照值相比，纹状体神经元中P物质mRNA表达无显著变化。慢性阿扑吗啡处理未显著改变脑啡肽mRNA表达，但在中脑纹状体系统6-OHDA诱导损伤后，每个细胞的表达比对照水平平均增加约130%。在有6-OHDA损伤并接受阿扑吗啡处理的动物中，脑啡肽mRNA也升高，但未显著高于仅由损伤产生的水平。这些数据表明，中脑纹状体多巴胺能系统对强啡肽、脑啡肽和P物质的表达有不同的调节作用，并且进一步表明这种调节发生的机制对于这三个肽家族可能有所不同。
