ALDH1 mRNA: presence in human dopamine neurons and decreases in substantia nigra in Parkinson's disease and in the ventral tegmental area in schizophrenia
ALDH1 mRNA: presence in human dopamine neurons and decreases in substantia nigra in Parkinson's disease and in the ventral tegmental area in schizophrenia
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DOI：
10.1016/j.nbd.2003.09.001
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发表时间：
2003-12-01
影响因子：
6.1
通讯作者：
Olson, L
中科院分区：
文献类型：
--
作者：
Galter, D;Buervenich, S;Olson, L
多巴胺（DA）神经元在帕金森病中会退化，并且在精神分裂症所见的精神病状态下，多巴胺神经传递可能会受到影响。因此，了解参与DA代谢的酶的调节机制可能会为这些严重疾病带来新的治疗策略。我们通过对人死后组织材料中的DA神经元进行原位杂交，研究了可能参与DA降解的胞质醛脱氢酶（ALDH1）的mRNA表达。同时对甘油醛 - 3 - 磷酸脱氢酶（GAPDH）、神经元特异性烯醇化酶、酪氨酸羟化酶、多巴胺转运体和多巴胺β - 羟化酶进行标记，以确保组织样本的适用性并识别所有多巴胺神经元。发现ALDH1在对照组的黑质（SN）和腹侧被盖区（VTA）的DA细胞中高度特异性表达。在帕金森病中，黑质致密部存活的神经元中ALDH1表达显著降低，但在VTA中的神经元中未见降低。在患有精神分裂症的患者中，我们发现黑质的DA细胞中ALDH1表达处于正常水平，但在VTA的DA细胞中表达水平显著降低。我们得出结论，ALDH1在人脑中脑多巴胺神经元中强烈且特异性表达，并且在两种所研究的人类疾病中，ALDH1的低表达水平与DA神经元功能障碍相关。（C）2003年爱思唯尔公司。保留所有权利。
Dopamine (DA) neurons degenerate in Parkinson's disease and dopamine neurotransmission may be affected in psychotic states seen in schizophrenia. Understanding the regulation of enzymes involved in DA metabolism may therefore lead to new treatment strategies for these severe conditions. We investigated mRNA expression of the cytosolic aldehyde dehydrogenase (ALDH1), presumably involved in DA degradation, by in situ hybridization in DA neurons of human postmortem material. Parallel labeling for GAPDH, neuron-specific enolase, tyrosine hydroxylase, dopamine transporter, and dopamine P-hydroxylase was used to ensure suitability of tissue specimen and to identify all dopamine neurons. ALDH1 was found to be expressed highly and specifically in DA cells of both substantia nigra (SN) and the ventral tegmental area (VTA) of controls. A marked reduction of ALDH1 expression was seen in surviving neurons of SN pars compacta but not of those in the VTA in Parkinson's disease. In patients suffering from schizophrenia we found ALDH1 expression at normal levels in DA cells of SN but at significantly reduced levels in those of the VTA. We conclude that ALDH1 is strongly and specifically expressed in human mesencephalic dopamine neurons and that low levels of ALDH1 expression correlate with DA neuron dysfunction in the two investigated human conditions. (C) 2003 Elsevier Inc. All rights reserved.