D1 AND D2 DOPAMINE RECEPTOR REGULATED GENE-EXPRESSION OF STRIATONIGRAL AND STRIATOPALLIDAL NEURONS
D1 AND D2 DOPAMINE RECEPTOR REGULATED GENE-EXPRESSION OF STRIATONIGRAL AND STRIATOPALLIDAL NEURONS
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DOI：
10.1126/science.2147780
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发表时间：
1990-12-07
期刊：
影响因子：
56.9
通讯作者：
SIBLEY, DR
中科院分区：
文献类型：
--
作者：
GERFEN, CR;ENGBER, TM;SIBLEY, DR
纹状体是大脑基底神经节的主要组成部分，部分受来自黑质的多巴胺能输入的调节。严重的运动障碍是由帕金森病患者纹状体多巴胺的丧失引起的。6-羟多巴胺（6-OHDA）引起的黑质纹状体多巴胺通路病变的大鼠作为帕金森病的模型，显示纹状体对白球和黑质的两个主要输出系统的基因表达改变。纹状体神经元显示6-OHDA.sbd。诱导其编码D2多巴胺受体和脑啡肽的信使（mrna）的特异性表达升高，随后用D2激动剂喹匹罗持续治疗可逆转。相反，纹状体神经元显示6-OHDA.sbd。导致编码D1多巴胺受体和P物质的mrna特异性表达降低，随后每日注射D1激动剂SKF-38393可逆转这一现象。这种治疗也增加了纹状体神经元的肌啡肽mRNA。因此，多巴胺对纹状体和纹状体神经元的差异作用分别由它们的D1和多巴胺受体亚型的特异性表达介导。
The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson''s disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson''s disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopalidal neurons show a 6-OHDA.sbd.induced elevation in their specific expression of messenger (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA.sbd.induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and dopamine receptor subtypes, respectively.