Department of Neurology, Chang Gung Memorial Hospital, Taipei 10507, Taiwan.
Brain. 2011 Aug;134(Pt 8):2312-20. doi: 10.1093/brain/awr158. Epub 2011 Jul 8.
Levodopa-induced dyskinesia is a major complication of long-term dopamine replacement therapy for Parkinson's disease that becomes increasingly problematic in advanced Parkinson's disease. Although the cause of levodopa-induced dyskinesias is still unclear, recent work in animal models of the corticostriatal system has suggested that levodopa-induced dyskinesias might result from abnormal control of synaptic plasticity. In the present study, we aimed to explore control of plasticity in patients with Parkinson's disease with and without levodopa-induced dyskinesias by taking advantage of a newly developed protocol that tests depotentiation of pre-existing long-term potentiation-like synaptic facilitation. Long-term potentiation-like plasticity and its reversibility were studied in the motor cortex of 10 healthy subjects, 10 patients with Parkinson's disease and levodopa-induced dyskinesias, who took half of the regular dose of levodopa and 10 patients with Parkinson's disease without levodopa-induced dyskinesias, who took either half or the full dose of levodopa. Patients with Parkinson's disease without levodopa-induced dyskinesias had normal long-term potentiation- and depotentiation-like effects when they took their full dose of levodopa, but there was no long-term potentiation-like effect when they were on half dose of levodopa. In contrast, patients with levodopa-induced dyskinesias could be successfully potentiated when they were on half their usual dose of levodopa; however, they were unresponsive to the depotentiation protocol. The results suggest that depotentiation is abnormal in the motor cortex of patients with Parkinson's disease with levodopa-induced dyskinesias and that their long-term potentiation-like plasticity is more readily affected by administration of levodopa than their clinical symptoms.
左旋多巴诱导的运动障碍是帕金森病长期多巴胺替代治疗的主要并发症，在晚期帕金森病中变得越来越成问题。尽管左旋多巴诱导的运动障碍的原因仍不清楚，但皮质纹状体系统动物模型的最新研究表明，左旋多巴诱导的运动障碍可能是由于突触可塑性的异常控制所致。在本研究中，我们旨在通过利用新开发的测试预先存在的长时程增强样突触易化去敏的方案，探索有无左旋多巴诱导的运动障碍的帕金森病患者的可塑性控制。在 10 名健康受试者、10 名服用半量常规左旋多巴剂量且伴有左旋多巴诱导的运动障碍的帕金森病患者和 10 名未伴有左旋多巴诱导的运动障碍且服用半量或全量左旋多巴的帕金森病患者的运动皮层中研究了长时程增强样可塑性及其可逆性。当服用全量左旋多巴时，无左旋多巴诱导的运动障碍的帕金森病患者具有正常的长时程增强和去敏样效应，但服用半量左旋多巴时则没有长时程增强样效应。相比之下，服用半量常规左旋多巴剂量的伴有左旋多巴诱导的运动障碍的患者可以成功地增强，但对去敏方案没有反应。结果表明，伴有左旋多巴诱导的运动障碍的帕金森病患者的运动皮层去敏异常，其长时程增强样可塑性更容易受到左旋多巴给药的影响，而不是其临床症状。
