Pifl C, Schingnitz G, Hornykiewicz O
Institute of Biochemical Pharmacology, University of Vienna, Austria.
Neurosci Lett. 1988 Oct 5;92(2):228-33. doi: 10.1016/0304-3940(88)90066-3.
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.
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。