Smith R D, Zhang Z, Kurlan R, McDermott M, Gash D M
Department of Neurobiology, University of Rochester School of Medicine and Dentistry, NY 14642.
Neuroscience. 1993 Jan;52(1):7-16. doi: 10.1016/0306-4522(93)90176-g.
The non-human primate models of Parkinson's disease which have been developed using the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine) have proven to be either unstable or variable, or to display only a limited subset of parkinsonian features. The present study examined a new two-stage lesion approach in which MPTP was administered via the carotid arteries. The first infusion through one artery produced a hemiparkinsonian state and was followed several months later by a second MPTP infusion into the contralateral carotid artery to induce bilateral parkinsonism. Animals receiving lesions were evaluated using a battery of tests which included a monkey parkinsonism rating scale, a movement time-task and continuous monitoring of home cage activity. All animals monitored showed significant decreases in activity levels of up to 95% following the second lesion. These decreased activity levels remained stable throughout the observation period of up to 12 months postlesion. In addition to the decreased home cage activity, bilaterally lesioned animals displayed bilateral parkinsonian features including akinesia, bradykinesia, rigidity, tremor and balance and gait disturbances which were stable, following an acute period of up to 45 days, for the remainder of the study. Administration of levodopa increased activity levels and reduced motor dysfunctions. Thus, a two-stage bilateral lesion approach, utilizing the neurotoxin MPTP, appears to provide a less variable and relatively stable model of bilateral Parkinson's disease in nonhuman primates. Treated animals display the cardinal features of parkinsonism and respond appropriately to the standard antiparkinsonian drug, levodopa.
使用神经毒素MPTP（1-甲基-4-苯基-1,2,3,6-四氢吡啶）开发的帕金森病非人灵长类动物模型已被证明要么不稳定、要么存在个体差异，要么仅表现出有限的帕金森病特征子集。本研究考察了一种新的两阶段损伤方法，即通过颈动脉给予MPTP。经一条动脉首次注射导致偏侧帕金森病状态，数月后对侧颈动脉进行第二次MPTP注射以诱发双侧帕金森病。接受损伤的动物通过一系列测试进行评估，包括猴子帕金森病评分量表、运动时间任务以及对笼内活动的持续监测。所有监测的动物在第二次损伤后活动水平显著下降高达95%。在损伤后长达12个月的观察期内，这些降低的活动水平保持稳定。除了笼内活动减少外，双侧损伤的动物还表现出双侧帕金森病特征，包括运动不能、运动迟缓、僵硬、震颤以及平衡和步态障碍，在长达45天的急性期后，这些特征在研究的剩余时间内保持稳定。给予左旋多巴可提高活动水平并减少运动功能障碍。因此，利用神经毒素MPTP的两阶段双侧损伤方法似乎能在非人灵长类动物中提供一个变异性较小且相对稳定的双侧帕金森病模型。接受治疗的动物表现出帕金森病的主要特征，并对标准抗帕金森病药物左旋多巴有适当反应。
