Department of Translational Neuroscience, College of Human Medicine, Michigan State University;
Department of Translational Neuroscience, College of Human Medicine, Michigan State University.
J Vis Exp. 2021 Oct 14(176). doi: 10.3791/62970.
Levodopa (L-DOPA) remains the gold-standard therapy used to treat Parkinson's disease (PD) motor symptoms. However, unwanted involuntary movements known as L-DOPA-induced dyskinesias (LIDs) develop with prolonged use of this dopamine precursor. It is estimated that the incidence of LIDs escalates to approximately 90% of individuals with PD within 10-15 years of treatment. Understanding the mechanisms of this malady and developing both novel and effective anti-dyskinesia treatments requires consistent and accurate modeling for pre-clinical testing of therapeutic interventions. A detailed method for reliable induction and comprehensive rating of LIDs following 6-OHDA-induced nigral lesioning in a rat model of PD is presented here. Dependable LID assessment in rats provides a powerful tool that can be readily utilized across laboratories to test emerging therapies focused on reducing or eliminating this common treatment-induced burden for individuals with PD.
左旋多巴(L-DOPA)仍然是治疗帕金森病(PD)运动症状的金标准疗法。然而,随着这种多巴胺前体的长期使用,会出现不想要的不自主运动,称为左旋多巴诱导的运动障碍(LIDs)。据估计,在接受治疗 10-15 年内,大约 90%的 PD 患者会出现 LIDs。为了了解这种疾病的机制并开发新的、有效的抗运动障碍治疗方法,需要对治疗干预措施进行一致和准确的临床前建模。本文介绍了一种在 PD 大鼠模型中,通过 6-OHDA 诱导黑质损伤可靠地诱导和全面评估 LIDs 的详细方法。在大鼠中进行可靠的 LID 评估提供了一个强大的工具,可以在各个实验室中轻松用于测试针对减少或消除 PD 患者常见治疗相关负担的新兴疗法。