Objective and quantitative evaluation of motor function in a monkey model of Parkinson's disease
Objective and quantitative evaluation of motor function in a monkey model of Parkinson's disease
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DOI：
10.1016/j.jneumeth.2010.05.009
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发表时间：
2010-07
影响因子：
3
通讯作者：
H. Saiki;Takuya Hayashi;R. Takahashi;J. Takahashi
中科院分区：
文献类型：
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作者：
H. Saiki;Takuya Hayashi;R. Takahashi;J. Takahashi
用1-甲基-4-苯基-1，2，5，6-四氢吡啶（MPTP）治疗的猴是目前帕金森病（PD）的最佳动物模型，并已被广泛用于生理和药理学研究。然而，客观和定量的评估尚未建立分级他们的运动行为。为了开发一种无偏的评价方法，我们进行了基于视频的评估，使用定性评分量表，并进行了全身MPTP治疗的猴中多巴胺（DA）转运蛋白结合的体内研究。基于视频的自发运动分析清楚地表明了与定性评分的显着相关性。通过[11 C]-CFT-PET对DA转运体（DAT）功能的评估表明，与正常动物相比，MPTP处理的动物在双侧纹状体中表现出CFT结合减少，特别是在壳核和尾状核的背侧部分。在MPTP治疗的猴子中，无偏见的PET分析显示，中脑中的CFT结合与定性评分或自发运动量之间存在显著相关性。这些结果表明，基于视频的分析可以是一个可靠的工具，MPTP治疗的猴子的运动功能障碍的客观和定量评价，此外，在中脑的DAT功能也可能是重要的评价。
Monkeys treated with 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) are currently the best animal model for Parkinson's disease (PD) and have been widely used for physiological and pharmacological investigations. However, objective and quantitative assessments have not been established for grading their motor behaviors. In order to develop a method for an unbiased evaluation, we performed a video-based assessment, used qualitative rating scales, and carried out an in vivo investigation of dopamine (DA) transporter binding in systemically MPTP-treated monkeys. The video-based analysis of spontaneous movement clearly demonstrated a significant correlation with the qualitative rating score. The assessment of DA transporter (DAT) function by [11C]-CFT-PET showed that, when compared with normal animals, the MPTP-treated animals exhibited decreased CFT binding in the bilateral striatum, particularly in the dorsal part in the putamen and caudate. Among the MPTP-treated monkeys, an unbiased PET analysis revealed a significant correlation between CFT binding in the midbrain and qualitative rating scores or the amount of spontaneous movements. These results indicate that a video-based analysis can be a reliable tool for an objective and quantitative evaluation of motor dysfunction of MPTP-treated monkeys, and furthermore, that DAT function in the midbrain may also be important for the evaluation.