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有症状的和恢复后的MPTP处理猫纹状体的神经化学评估

Neurochemical evaluation of the striatum in symptomatic and recovered MPTP-treated cats.

作者信息

Schneider J S, Rothblat D S

机构信息

Department of Neurology, Hahnemann University School of Medicine, Philadelphia, PA 19102.

出版信息

Neuroscience. 1991;44(2):421-9. doi: 10.1016/0306-4522(91)90066-w.

DOI:10.1016/0306-4522(91)90066-w
PMID:1944893
Abstract

Striatal neurochemistry and motor activity were assessed in cats treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and killed either when symptomatic for a Parkinson-like motor disorder or six weeks later, when showing significant motor recovery. The results of striatal neurochemical analyses showed distinct regional differences in susceptibility to MPTP-induced damage, with dorsal striatal regions generally more severely affected than ventral striatal regions. Symptomatic animals had more severe dopamine loss in all striatal regions than did recovered animals. The dorsal lateral caudate, the cat's sensorimotor striatum, had the largest dopamine depletion in the symptomatic animals (99%) and the least recovery in recovered animals (94% depletion). In contrast, the nucleus accumbens had a 94% dopamine depletion in symptomatic animals and only a 34% depletion in recovered animals. In addition to increases in dopamine levels and dopamine utilization in the striatum in recovered animals, significant increases in serotonin levels and serotonin utilization were also observed. Therefore, motor recovery may have been due to either or both of these neurochemical changes. The fact that the cat develops Parkinson-like motor symptoms but that they are not persistent may make this an interesting model in which to study the role of dopamine in motor function and to study compensatory mechanisms of the damaged dopamine system.

摘要

对用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)处理的猫的纹状体神经化学和运动活动进行了评估。这些猫在出现帕金森样运动障碍症状时或六周后(此时显示出明显的运动恢复)被处死。纹状体神经化学分析结果显示,对MPTP诱导损伤的易感性存在明显的区域差异,背侧纹状体区域通常比腹侧纹状体区域受影响更严重。有症状的动物在所有纹状体区域的多巴胺损失比恢复的动物更严重。背外侧尾状核,即猫的感觉运动纹状体,在有症状的动物中多巴胺耗竭最大(99%),在恢复的动物中恢复最少(94%的耗竭)。相比之下,伏隔核在有症状的动物中多巴胺耗竭为94%,在恢复的动物中仅为34%。除了恢复的动物纹状体中多巴胺水平和多巴胺利用率增加外,还观察到血清素水平和血清素利用率显著增加。因此,运动恢复可能是由于这些神经化学变化中的一种或两种。猫出现帕金森样运动症状但不持续这一事实可能使其成为研究多巴胺在运动功能中的作用以及研究受损多巴胺系统补偿机制的一个有趣模型。

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