Dopamine D-1 and D-2 receptor gene expression in the striatum in Huntington's disease

Dopamine D-1 and D-2 receptor gene expression in the striatum in Huntington's disease
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DOI:
10.1002/ana.410420213
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发表时间:
1997-08-01
影响因子:
11.2
通讯作者:
Emson, PC
Emson, PC
中科院分区:
医学1区
文献类型:
--
作者:
Augood, SJ;Faull, RLM;Emson, PC

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应用定量原位杂交技术研究了正常人和经遗传学和病理学证实的亨廷顿病(HD)患者死后尾状核多巴胺D-1和D-2受体mRNA的表达。根据Vonsattel量表,根据纹状体神经病理学的严重程度对HD病例进行分类(0-4)。对于HD 0级病例,与对照组相比,观察到D-1和D-2 mRNA阳性细胞数量显著减少;然而,每个剩余细胞中两种受体mRNA的丰度均在对照范围内。对于D-2受体mRNA,可检测到的D-2阳性中型细胞的数量随着病理学的增加而减少;这种减少伴随着每个细胞的D-1信号强度的逐渐降低。相比之下,对于D-1受体mRNA,尽管检测到的D-1 mRNA阳性细胞数量减少,但HD I级病例中D-1 mRNA的平均细胞表达显着减少,然后随着病理学的增加而增加(相对于I级病例),这可能反映了表达D-1的纹状体中间神经元的相对存活。这些研究结果的影响,提供进一步的信息,在HD的神经退行性过程中进行了讨论。
The cellular expression of dopamine D-1 and D-2 receptor mRNAs was investigated in the postmortem human caudate nucleus of control cases and genetically and pathologically confirmed cases of Huntington's disease (HD) by using quantitative in situ hybridization. The HD cases were categorized (0-4) by severity of striatal neuropathology according to the Vonsattel scale. For the HD grade 0 case, a pronounced reduction in the number of D-1 and D-2 mRNA-positive cells was observed compared with controls; however, the abundance of both receptor mRNAs per remaining cell was within the control range. For D-2 receptor mRNA, the number of detectable D-2-positive medium-sized cells decreased with increasing pathology; this decrease was accompanied by a gradual reduction in the intensity of D-1 signal per cell. By contrast, for D-1 receptor mRNA, despite a decrease in the number of D-1 mRNA-positive cells detected, the average cellular expression of D-1 mRNA was markedly reduced in the HD grade I case and then increased (relative to the grade I case) with increasing pathology, presumably reflecting the relative survival of D-1-expressing striatal interneurons. The implications of these findings for providing further information on the neurodegenerative process in HD are discussed.