THE TOXICITY OF MPTP TO DOPAMINE NEURONS IN CULTURE IS REDUCED AT HIGH-CONCENTRATIONS
THE TOXICITY OF MPTP TO DOPAMINE NEURONS IN CULTURE IS REDUCED AT HIGH-CONCENTRATIONS
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DOI：
10.1016/0304-3940(87)90673-2
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发表时间：
1987-08-18
影响因子：
2.5
通讯作者：
MYTILINEOU, C
中科院分区：
文献类型：
--
作者：
FRIEDMAN, L;MYTILINEOU, C
在大鼠胚胎中脑分离细胞培养中研究了MPTP对多巴胺（DA）神经元的毒性。培养物暴露于MPTP （0.1 ~ 200.mu）。M)孵育7天，用。alpha孵育后用儿茶酚胺组织荧光分析。酪氨酸羟化酶（T-OH）免疫细胞化学和[3H]DA摄取。在较低的浓度范围内（0.1 - 5 μ m之间）用MPTP处理。M)导致[3H]DA的摄取呈剂量依赖性减少，在5 μ M时效果最大。MPTP浓度进一步增加（从10亩增加到200亩）。M)导致毒性作用的逐渐衰减。暴露在200亩。mmptp对[3H]DA的摄取没有显著减少。儿茶酚胺组织荧光和T-OH免疫细胞化学显示，在10和100 .mu的MPTP浓度下，DA神经元的存活率增加。注射米MPTP药物。在培养中，MPTP被证明是一种有效的抑制MPP+被DA神经元摄取的抑制剂。在100或200亩的土地上。在MPTP中，MPP+的摄取减少到对照水平的20%以下。因此，高浓度MPTP毒性的降低可以解释为，至少在一定程度上，在高浓度MPTP存在下，MPP+ （MPTP氧化的有毒代谢物）的摄取受到抑制。
The toxicity of MPTP to dopamine (DA) neurons was studied in dissociated cell cultures from rat embryo mesencephalon. The cultures were exposed to MPTP (from 0.1 to 200 .mu.M) for 7 days and were analyzed by catecholamine histofluorescence after incubation with .alpha.-methylnorepinephrine, by tyrosine hydroxylase (T-OH) immunocytochemistry and by [3H]DA uptake. Treatment with MPTP at the lower range of concentrations (between 0.1 and 5 .mu.M) resulted in a dose-dependent reduction of the uptake of [3H]DA, which had a maximum effect at 5 .mu.M. Further increase in the concentration of MPTP (from 10 to 200 .mu.M) resulted in progressive attenuation of the toxic effect. Exposure to 200 .mu.M MPTP did not produce significant reduction in the uptake of [3H]DA. Increased survival of DA neurons at the higher concentrations of MPTP, was documented by catecholamine histofluorescence and by T-OH immunocytochemistry in cultures treated with 10 and 100 .mu.M MPTP. MPTP was shown to be a potent inhibitor of MPP+ uptake by DA neurons in culture. In the presence of 100 or 200 .mu.M MPTP, the uptake of MPP+ was reduced to less than 20% of control levels. Therefore, the reduction of MPTP toxicity at the high concentrations can be explained, at least in part, by the inhibition of the uptake of MPP+ (the toxic metabolite of MPTP oxidation) in the presence of high concentrations of MPTP.