Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, BMC F11, Sölvegatan 19, 22184 Lund, Sweden.
Parkinsonism Relat Disord. 2014 Jan;20 Suppl 1:S20-2. doi: 10.1016/S1353-8020(13)70008-7.
L-DOPA-induced dyskinesia (LID) is a major complication of the pharmacotherapy of Parkinson's disease (PD). Animal models of LID are essential for investigating pathogenic pathways and therapeutic targets. While non-human primates have been the preferred species for pathophysiological studies, mouse models of LID have been recently produced and characterized to facilitate molecular investigations. Most of these studies have used mice with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal projection sustaining treatment with L-DOPA for 1-4 weeks. Mice with complete medial forebrain bundle lesions have been found to develop dyskinetic movements of maximal severity associated with a pronounced post-synaptic supersensitivity of D1-receptor dependent signaling pathways throughout the striatum. In contrast, mice with striatal 6-OHDA lesions have been found to exhibit a variable susceptibility to LID and a regionally restricted post-synaptic supersensitivity. Genetic mouse models of PD have just started to be used for studies of LID, providing an opportunity to dissect the impact of genetic factors on the maladaptive neuroplasticity that drives the development of treatment-induced involuntary movements in PD.
左旋多巴诱导的运动障碍（LID）是帕金森病（PD）药物治疗的主要并发症。LID 的动物模型对于研究发病机制和治疗靶点至关重要。虽然非人类灵长类动物一直是用于生理病理学研究的首选物种，但最近已经产生并描述了 LID 的小鼠模型，以促进分子研究。这些研究大多使用单侧 6-羟多巴胺（6-OHDA）损伤黑质纹状体投射的小鼠，并持续接受左旋多巴治疗 1-4 周。研究发现，完全内侧前脑束损伤的小鼠会出现最严重的运动障碍，同时纹状体中 D1 受体依赖性信号通路的突触后超敏反应明显。相比之下，纹状体 6-OHDA 损伤的小鼠对 LID 的易感性不同，并且出现了局灶性的突触后超敏反应。PD 的遗传小鼠模型刚刚开始用于 LID 的研究，为研究遗传因素对驱动 PD 治疗诱导的不自主运动发展的适应性神经可塑性的影响提供了机会。
