Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education and Key Laboratory of Basic Pharmacology of Guizhou Province and Laboratory Animal Center, Zunyi Medical University, Zunyi, China.
Front Immunol. 2021 Jun 25;12:683577. doi: 10.3389/fimmu.2021.683577. eCollection 2021.
Dyskinesia is a serious complication of Parkinson's disease during levodopa (L-DOPA) treatment. The pathophysiology of L-DOPA-induced dyskinesia (LID) is complex and not fully illuminated. At present, treatment of dyskinesia is quite limited. Recent studies demonstrated neuroinflammation plays an important role in development of LID. Thus, inhibition of neuroinflammation might open a new avenue for LID treatment. Resveratrol (RES) is the most well-known polyphenolic stilbenoid and verified to possess a large variety of biological activities. DA neurotoxicity was assessed behavior test and DA neuronal quantification. The movement disorders of dyskinesia were detected by the abnormal involuntary movements scores analysis. Effects of RES on glial cells-elicited neuroinflammation were also explored. Data showed that RES attenuated dyskinesia induced by L-DOPA without affecting L-DOPA's anti-parkinsonian effects. Furthermore, RES generated neuroprotection against long term treatment of L-DOPA-induced DA neuronal damage. Meanwhile, RES reduced protein expression of dyskinesia molecular markers, ΔFOS B and ERK, in the striatum. Also, there was a strong negative correlation between DA system damage and ΔFOS B level in the striatum. In addition, RES inhibited microglia and astroglia activation in substantia nigra and subsequent inflammatory responses in the striatum during L-DOPA treatment. RES alleviates dyskinesia induced by L-DOPA and these beneficial effects are closely associated with protection against DA neuronal damage and inhibition of glial cells-mediated neuroinflammatory reactions.
运动障碍是左旋多巴(L-DOPA)治疗帕金森病的严重并发症。L-DOPA 诱导的运动障碍(LID)的病理生理学非常复杂,尚未完全阐明。目前,运动障碍的治疗方法相当有限。最近的研究表明神经炎症在 LID 的发展中起重要作用。因此,抑制神经炎症可能为 LID 的治疗开辟新途径。白藜芦醇(RES)是最著名的多酚类芪类物质,已被证实具有多种生物学活性。通过行为测试和 DA 神经元定量评估 DA 神经毒性。通过异常不自主运动评分分析检测运动障碍的运动障碍。还探讨了 RES 对神经胶质细胞引发的神经炎症的影响。数据表明,RES 减轻了 L-DOPA 诱导的运动障碍,而不影响 L-DOPA 的抗帕金森病作用。此外,RES 对 L-DOPA 诱导的 DA 神经元损伤的长期治疗产生了神经保护作用。同时,RES 降低了纹状体中运动障碍分子标志物 ΔFOS B 和 ERK 的蛋白表达。此外,纹状体中 DA 系统损伤与 ΔFOS B 水平之间存在很强的负相关。此外,RES 抑制了黑质中小胶质细胞和星形胶质细胞的激活以及 L-DOPA 治疗期间纹状体中的炎症反应。RES 减轻了 L-DOPA 诱导的运动障碍,这些有益作用与防止 DA 神经元损伤和抑制神经胶质细胞介导的神经炎症反应密切相关。