乙醇或乙醛会增强小鼠体内1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的神经毒性。

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice is enhanced by ethanol or acetaldehyde.

作者信息

Corsini G U, Zuddas A, Bonuccelli U, Schinelli S, Kopin I J

出版信息

Life Sci. 1987 Mar 2;40(9):827-32. doi: 10.1016/0024-3205(87)90030-0.

Abstract

Persistent neurochemical changes consistent with parkinsonism have been reported in brains of mice treated with repeated high doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We now report that ethanol or acetaldehyde potentiate MPTP-induced damage to mouse striatum. One hour after the combined treatments (ethanol and MPTP or acetaldehyde and MPTP), the animals exhibited a marked and long-lasting catatonic posture and then returned gradually to apparently normal locomotion. Seven days after MPTP administration, depletion of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in mouse striatum were further potentiated in the group of animals treated with ethanol. This effect was more evident when the treatment was repeated twice and was dose-dependent. Acetaldehyde was more potent than ethanol in enhancing MPTP neurotoxicity. A single exposure to acetaldehyde before and during MPTP treatment produced a very consistent fall of DA, DOPAC and HVA but not serotonin (5HT) or 5-hydroxyindoleacetic acid (5HIAA) in the striatum. This suggests that ethanol effects on MPTP neurotoxicity might be related to acetaldehyde formation.

摘要

据报道，用反复高剂量的1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理的小鼠大脑中存在与帕金森病一致的持续性神经化学变化。我们现在报告，乙醇或乙醛会增强MPTP对小鼠纹状体的损伤。联合处理（乙醇和MPTP或乙醛和MPTP）1小时后，动物表现出明显且持久的紧张性姿势，然后逐渐恢复到明显正常的运动状态。在给予MPTP 7天后，用乙醇处理的动物组中，小鼠纹状体中多巴胺（DA）、3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）的耗竭进一步加剧。当重复治疗两次时，这种效应更明显，且呈剂量依赖性。在增强MPTP神经毒性方面，乙醛比乙醇更有效。在MPTP治疗前和治疗期间单次接触乙醛会使纹状体中的DA、DOPAC和HVA非常一致地下降，但不会使血清素（5HT）或5-羟吲哚乙酸（5HIAA）下降。这表明乙醇对MPTP神经毒性的影响可能与乙醛的形成有关。