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神经毒素MPTP在恒河猴身上不会重现人类特发性帕金森病典型的纹状体多巴胺丧失的区域间模式。

The neurotoxin MPTP does not reproduce in the rhesus monkey the interregional pattern of striatal dopamine loss typical of human idiopathic Parkinson's disease.

作者信息

Pifl C, Schingnitz G, Hornykiewicz O

机构信息

Institute of Biochemical Pharmacology, University of Vienna, Austria.

出版信息

Neurosci Lett. 1988 Oct 5;92(2):228-33. doi: 10.1016/0304-3940(88)90066-3.

Abstract

Using high-pressure liquid chromatography with electrochemical detection, we measured dopamine (DA) and homovanillic acid (HVA) in caudate nucleus, putamen and substantia nigra in 4 untreated rhesus monkeys and 4 monkeys with permanent parkinsonism produced by repeated injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; total dose: 2.1-6.45 mg/kg, i.m.). MPTP consistently produced a severe striatal and nigral loss of DA and HVA and an increase in the ratio 'HVA/DA'. In this respect, MPTP mimicked the changes found in human Parkinson's disease (PD). However, MPTP lowered the DA in caudate (-99.6%) to the same degree as in putamen (-99.5%). This is in contrast to idiopathic PD where the caudate is significantly less affected by DA loss (-84%) than the putamen (-98%). Thus, in our rhesus monkeys MPTP failed to reproduce the interregional caudate-putamen gradient characteristic of idiopathic PD. The DA pattern produced by MPTP was similar to the DA loss in caudate (-98%) and putamen (-99%) observed in patients with postencephalitic parkinsonism.

摘要

我们采用带电化学检测的高压液相色谱法,测定了4只未经治疗的恒河猴以及4只因反复注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP;总剂量:2.1 - 6.45毫克/千克,肌肉注射)而导致永久性帕金森症的猴子尾状核、壳核和黑质中的多巴胺(DA)和高香草酸(HVA)。MPTP始终导致纹状体和黑质中DA和HVA严重缺失,以及“HVA/DA”比值升高。在这方面,MPTP模拟了人类帕金森病(PD)中发现的变化。然而,MPTP使尾状核中的DA降低了99.6%,与壳核中DA降低99.5%的程度相同。这与特发性PD相反,在特发性PD中,尾状核受DA缺失的影响(-84%)明显小于壳核(-98%)。因此,在我们的恒河猴中,MPTP未能重现特发性PD所特有的尾状核 - 壳核区域间梯度变化。MPTP产生的DA模式与脑炎后帕金森症患者尾状核(-98%)和壳核(-99%)中观察到的DA缺失相似。

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