A chronic MPTP model reproducing the slow evolution of Parkinson's disease: evolution of motor symptoms in the monkey
A chronic MPTP model reproducing the slow evolution of Parkinson's disease: evolution of motor symptoms in the monkey
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DOI：
10.1016/s0006-8993(97)00531-3
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发表时间：
1997-08-22
期刊：
影响因子：
2.9
通讯作者：
Gross, CE
中科院分区：
文献类型：
--
作者：
Bezard, E;Imbert, C;Gross, CE
1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)在人类和非人类灵长类动物中均可诱发帕金森病。现在已经开发了几种模型，但急性MPTP给药并不能始终如一地再现该病的所有临床特征。为了反映在人类病理学中观察到的缓慢进化，一个慢性中毒模型是必要的。本研究描述了猴子的一种慢性MPTP方案。6只猴子每天静脉注射MPTP(0.2 mg/kg)。直到他们在临床评定量表上达到8分以上(15.5天+/-1.1)。完全性帕金森病首次出现在第22天。左旋多巴试验(20毫克/公斤/次)缓解了运动异常(51%)，证明了这些障碍的帕金森病性质。组织学损伤再现了帕金森氏病中观察到的病变，酪氨酸羟化酶免疫反应性下降了90%。该模型对研究帕金森病末期的动态生理病理变化，进而研究新的神经保护疗法具有重要意义。(C)1997年爱思唯尔科学公司。
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to induce parkinsonism both in man and non-human primates. Several models have now been developed, but acute MPTP administration does not consistently reproduce all the clinical features of the disease. To mirror the slow evolution observed in human pathology, a chronic model of intoxication is necessary. The present study describes a chronic MPTP protocol in the monkey. Six monkeys received daily injections of MPTP (0.2 mg/kg i.v.) until they reached a score over 8 on the clinical rating scale (15.5 days +/- 1.1). Full parkinsonism was first obtained on the 22nd day. Levodopa testing (20 mg/kg per os) alleviated motor abnormalities (51%), proving the parkinsonian nature of these disturbances. Histological lesions reproduced those observed in Parkinson's disease with a decrease in tyrosine hydroxylase immunoreactivity of 90%. This model so could be of great interest for the study of the dynamic physiopathological changes which occur in Parkinson's disease end consequently for research on new neuroprotective therapies. (C) 1997 Elsevier Science B.V.