Basal Ganglia Pathophysiology Unit, Dept. Experimental Medical Science, Lund University, BMC F11, 221 84 Lund, Sweden.
Parkinsonism Relat Disord. 2009 Dec;15 Suppl 3:S59-63. doi: 10.1016/S1353-8020(09)70782-5.
The development of L-DOPA-induced dyskinesia (LID) is attributed to plastic responses triggered by dopamine (DA) receptor stimulation in the parkinsonian brain. This article reviews studies that have uncovered different levels of maladaptive plasticity in animal models of LID. Rats developing dyskinesia on chronic L-DOPA treatment show abnormal patterns of signaling pathway activation and synaptic plasticity in striatal neurons. In addition, these animals show a gene expression profile indicative of structural cellular plasticity, including pronounced upregulation of genes involved in extracellular matrix remodeling, neurite extension, synaptic vesicle trafficking, and endothelial and cellular proliferation. Structural changes of neurons and microvessels within the basal ganglia are currently being unraveled by detailed morphological analyses. The structural and functional adaptations induced by L-DOPA in the brain can be viewed as an attempt to meet increased metabolic demands and to boost cellular defense mechanisms. These homeostatic responses, however, also predispose to the appearance of dyskinesia and other complications during the course of the treatment.
左旋多巴诱导的运动障碍（LID）的发展归因于帕金森病大脑中多巴胺（DA）受体刺激引发的可塑性反应。本文综述了在 LID 动物模型中发现的不同水平的适应性不良可塑性的研究。在慢性左旋多巴治疗下出现运动障碍的大鼠在纹状体神经元中表现出信号通路激活和突触可塑性的异常模式。此外，这些动物表现出表明结构细胞可塑性的基因表达谱，包括涉及细胞外基质重塑、神经突延伸、突触小泡运输以及内皮和细胞增殖的基因的显著上调。目前正在通过详细的形态学分析揭示基底神经节内神经元和微血管的结构变化。L-DOPA 在大脑中诱导的结构和功能适应性可被视为满足增加的代谢需求和增强细胞防御机制的一种尝试。然而，这些内稳态反应也使运动障碍和治疗过程中的其他并发症更容易出现。
