Soghomonian J J, Chesselet M F
Department of Pharmacology, University of Pennsylvania, Philadelphia 19104.
Synapse. 1992 Jun;11(2):124-33. doi: 10.1002/syn.890110205.
The neurotransmitter gamma-aminobutyric acid (GABA) is present in efferent neurons of the striatum and of the pallidum, one of the main striatal target areas. Dopaminergic nigrostriatal neurons play a critical role in the regulation of GABAergic neurotransmission in the striatum. In the present study, we investigated their role in the regulation of glutamate-decarboxylase (GAD) mRNA expression in two divisions of the pallidum in rats: the globus pallidus and entopeduncular nucleus, equivalent to the external and internal pallidum, respectively, of primates. Dopaminergic neurons were lesioned by unilateral injections of 6-hydroxydopamine (6-OHDA) in the substantia nigra of adult rats. Two or 3 weeks after the lesion, frontal cryostat-cut sections of the brain were processed for in situ hybridization histochemistry with 35S-labeled RNA probes synthesized from cDNAs encoding two distinct isoforms of GAD of respective molecular weight 67,000 (GAD67) and 65,000 (GAD65). The number of labeled cells was determined, and intensity of labeling in individual cells was analyzed by computerized image analysis on emulsion radioautographs. In the globus pallidus, the number of labeled neurons and intensity of labeling per cell were increased on the side ipsilateral to the lesion as compared with control rats in sections hybridized with the GAD67 RNA probe. No changes were detected on the side contralateral to the lesion or in the levels of labeling for GAD65 mRNA. Confirming previous data, the level of labeling for GAD65 mRNA was much higher than for GAD67 mRNA in the entopeduncular nucleus of control rats. In rats with a 6-OHDA lesion, labeling for both GAD67 and GAD65 mRNAs was decreased on the side contralateral, but not ipsilateral, to the lesion, as compared with control rats. The results show that lesions of the nigrostriatal pathway in rats affect the levels of mRNAs encoding two distinct isoforms of GAD in neurons of the globus pallidus and entopeduncular nucleus differently. In addition, results in the entopeduncular nucleus further support a bilateral effect of unilateral dopaminergic lesions.
神经递质γ-氨基丁酸（GABA）存在于纹状体以及纹状体主要靶区之一苍白球的传出神经元中。多巴胺能黑质纹状体神经元在调节纹状体中的GABA能神经传递方面起着关键作用。在本研究中，我们调查了它们在大鼠苍白球两个分区（即苍白球和内苍白球，分别相当于灵长类动物的外侧苍白球和内侧苍白球）中对谷氨酸脱羧酶（GAD）mRNA表达调节的作用。通过向成年大鼠黑质单侧注射6-羟基多巴胺（6-OHDA）来损伤多巴胺能神经元。损伤后2或3周，将大脑额叶低温恒温器切片用于原位杂交组织化学，使用从编码分子量分别为67,000（GAD67）和65,000（GAD65）的两种不同GAD同工型的cDNA合成的35S标记RNA探针。确定标记细胞的数量，并通过对乳胶放射自显影片进行计算机图像分析来分析单个细胞中的标记强度。在与GAD67 RNA探针杂交的切片中，与对照大鼠相比，苍白球中标记神经元的数量和每个细胞的标记强度在损伤同侧增加。在损伤对侧或GAD65 mRNA的标记水平上未检测到变化。与先前数据一致，对照大鼠内苍白球中GAD65 mRNA的标记水平远高于GAD67 mRNA。在6-OHDA损伤的大鼠中，与对照大鼠相比，损伤对侧而非同侧的GAD67和GAD65 mRNA的标记均降低。结果表明，大鼠黑质纹状体通路损伤对苍白球和内苍白球神经元中编码两种不同GAD同工型的mRNA水平有不同影响。此外，内苍白球的结果进一步支持了单侧多巴胺能损伤的双侧效应。
