A PRIMATE MODEL OF PARKINSONISM - SELECTIVE DESTRUCTION OF DOPAMINERGIC-NEURONS IN THE PARS COMPACTA OF THE SUBSTANTIA NIGRA BY N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE
A PRIMATE MODEL OF PARKINSONISM - SELECTIVE DESTRUCTION OF DOPAMINERGIC-NEURONS IN THE PARS COMPACTA OF THE SUBSTANTIA NIGRA BY N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE
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DOI：
10.1073/pnas.80.14.4546
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
KOPIN, IJ
中科院分区：
文献类型：
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作者：
BURNS, RS;CHIUEH, CC;KOPIN, IJ
自行静脉注射非法药物制剂后出现类似于特发性帕金森病的综合征，其中 N-甲基-4-苯基-1,2,3,6-四氢吡啶 (NMPTP) 可能是造成毒性的原因。在本研究中，我们表明，给恒河猴静脉注射 NMPTP 会产生帕金森病（运动不能、强直、姿势性震颤、屈曲姿势、眼睑闭合、流口水）等疾病，而注射左旋多巴可以逆转这种疾病。 NMPTP 治疗减少多巴胺的释放，多巴胺积聚在黑质上方黑质纹状体通路中肿胀、扭曲的轴突中，随后黑质致密部神经细胞严重损失，纹状体的多巴胺含量显着减少。 NMPTP 产生的病理和生化变化与帕金森病患者的已知变化相似。因此，经过 NMPTP 治疗的猴子提供了一个模型，可用于检查帕金森病的机制和探索帕金森病的治疗方法。
A syndrome similar to idiopathic parkinsonism developed after intravenous self-administration of an illicit drug preparation in which N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) might have been responsible for the toxicity. In the present study we show that intravenous administration of NMPTP to the rhesus monkey produces a disorder like parkinsonism (akinesia, rigidity, postural tremor, flexed posture, eyelid closure, drooling) that is reversed by the administration of L-dopa. NMPTP treatment decreases the release of dopamine and dopamine accumulates in swollen, distorted axons in the nigrostriatal pathway just above the substantia nigra, followed by severe nerve cell loss in the pars compacta of the substantia nigra and a marked reduction in the dopamine content of the striatum. The pathological and biochemical changes produced by NMPTP are similar to the well-established changes in patients with parkinsonism. Thus, the NMPTP-treated monkey provides a model that can be used to examine mechanisms and explore therapies of parkinsonism.