DIFFERENTIAL EXPRESSION OF TYROSINE-HYDROXYLASE AND MEMBRANE DOPAMINE TRANSPORTER GENES IN SUBPOPULATIONS OF DOPAMINERGIC-NEURONS OF THE RAT MESENCEPHALON
DIFFERENTIAL EXPRESSION OF TYROSINE-HYDROXYLASE AND MEMBRANE DOPAMINE TRANSPORTER GENES IN SUBPOPULATIONS OF DOPAMINERGIC-NEURONS OF THE RAT MESENCEPHALON
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DOI：
10.1016/0169-328x(94)90029-9
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发表时间：
1994-03-01
期刊：
影响因子：
--
通讯作者：
AGID, Y
中科院分区：
文献类型：
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作者：
BLANCHARD, V;RAISMANVOZARI, R;AGID, Y
黑质致密部 (SNC) 和腹侧被盖区 (VTA) 的多巴胺能 (DA) 细胞在形态、生物化学和对病理过程的易感性方面表现出差异。神经元多巴胺浓度在很大程度上受酪氨酸羟化酶（TH）（多巴胺合成的限速酶）和多巴胺再摄取系统的调节。在本研究中，利用原位杂交和免疫放射自显影技术，在大鼠腹侧中脑的 4 个任意亚区域（外侧、中部、内侧 SNC 和 VTA）的细胞水平上对 TH 蛋白、TH mRNA 和多巴胺膜转运蛋白 (DAT) mRNA 进行定量。中脑神经元中TH蛋白和TH mRNA的标记分布几乎是重叠的并且与DAT mRNA的分布接近。与其他亚区域相比，SNC 外侧部分的 TH 蛋白、TH mRNA 和 DAT mRNA 细胞表达值较低。 TH 和 DAT 表达在 SNC 中相关，但在 VTA 中不相关。事实上，与中部和内侧 SNC 相比，该区域的 DA 细胞表达低水平的 DAT mRNA。这些结果表明中脑细胞群体中 DA 代谢存在异质性。 VTA 神经元中 DAT 基因的表达相对较低，表明多巴胺再摄取能力效率较低，这可能部分解释了帕金森病和 MPTP 治疗动物中中脑边缘系统相对较少的原因。
Dopaminergic (DA) cells of the substantia nigra pars compacta (SNC) and the ventral tegmental area (VTA) display differences in their topography, biochemistry and susceptibility to pathological processes. Neuronal dopamine concentration is regulated in large part by tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine synthesis, and by the dopamine reuptake system. In the present study, TH protein, TH mRNA and dopamine membrane transporter (DAT) mRNA were quantified at cellular level in 4 arbitrary subregions of the rat ventral mesencephalon (lateral, middle, medial SNC and VTA), using in situ hybridization and immunoautoradiography. The distribution of labelling for TH protein and TH mRNA was almost superimposable and close to that of DAT mRNA in mesencephalic neurons. Lower values of cellular expression in TH protein, TH mRNA and DAT mRNA were observed in the lateral part of the SNC compared to the other subregions. TH and DAT expression were correlated in SNC but not in VTA. Indeed DA cells in this region expressed low levels of DAT mRNA in comparison to the middle and medial SNC. These results suggest a heterogeneity of DA metabolism among populations of mesencephalic cells. The relative lower expression of the DAT gene in VTA neurons suggests a less efficient dopamine reuptake capacity, which may partly account for the relative sparing of the mesolimbic system reported in Parkinson's disease and MPTP-treated animals.