Levodopa-induced dyskinesia in MPTP-treated macaques is not dependent on the extent and pattern of nigrostrial lesioning
Levodopa-induced dyskinesia in MPTP-treated macaques is not dependent on the extent and pattern of nigrostrial lesioning
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DOI：
10.1111/j.1460-9568.2005.04196.x
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发表时间：
2005-07-01
影响因子：
3.4
通讯作者：
Bezard, E
中科院分区：
文献类型：
--
作者：
Guigoni, C;Dovero, S;Bezard, E
黑质纹状体去神经支配的程度被认为在左旋多巴诱导的运动障碍的发生中起作用。然而，一些帕金森病患者在长期治疗后并没有出现运动障碍，这就增加了一种可能性，即去神经支配的方式与病变的程度一样重要，是一个危险因素。在这里，我们研究的程度和模式的黑质纹状体去神经在一个同质人口的帕金森病猕猴长期治疗左旋多巴。根据病变特征，无法区分非运动障碍动物与运动障碍动物。事实上，酪氨酸羟化酶（TH）的免疫阳性神经元的数量在黑质pars延髓，纹状体多巴胺转运蛋白（DAT）的结合和TH免疫染色，以及整体TH纹状体含量测定Western印迹法是相同的。此外，通过详细分析TH和DAT免疫阳性纹状体纤维评估的病变模式在所有功能象限和所有考虑的头尾侧水平都相当。这些数据表明，黑质纹状体病变的程度和模式都不足以解释左旋多巴诱导的运动障碍的发生。
The extent of nigrostriatal denervation is presumed to play a role in the genesis of levodopa-induced dyskinesia. Yet some parkinsonian patients who have been treated over a long period do not develop dyskinesia, raising the possibility that the pattern of denervation is as important as the extent of lesioning as a risk factor. Here we study the extent and pattern of nigrostriatal denervation in a homogeneous population of parkinsonian macaque monkeys chronically treated with levodopa. Based on the characteristics of the lesioning, non-dyskinetic animals could not be differentiated from those with dyskinesia. Indeed, the number of tyrosine-hydroxylase (TH)-immunopositive neurons in the substantia nigra pars compacta, striatal dopamine transporter (DAT) binding and TH immunostaining, as well as the overall TH striatal content measured by Western blotting were identical. Moreover, the patterns of lesioning assessed by a detailed analysis of the TH- and DAT-immunopositive striatal fibers were comparable in all functional quadrants and at all rostro-caudal levels considered. These data indicate that neither the extent nor the pattern of nigrostriatal lesioning are sufficient to explain the occurrence of levodopa-induced dyskinesia.