School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Department of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, CEP: 14049-900, Brazil.
J Neural Transm (Vienna). 2020 Oct;127(10):1359-1367. doi: 10.1007/s00702-020-02240-9. Epub 2020 Aug 14.
Levodopa-induced dyskinesias (LID) in Parkinson's disease (PD) are frequent complications, and the endocannabinoid system has a role on its pathophysiology. To test the hypothesis that the functioning of the endocannabinoid system would be altered in PD and in LID by measuring plasma and CSF levels of α-N-arachidonoylethanolamine (AEA) and 2-arachidonoyl-glycerol (2-AG) in patients with PD with and without LID and in healthy controls. Blood and CSF samples were collected from 20 healthy controls, 23 patients with PD without LID, and 24 patients with PD with LID. The levels of AEA and 2-AG were measured using a highly sensitive column switching ultrahigh-performance liquid chromatography-tandem mass spectrometry method. When pooled together, patients with PD had lower plasma and CSF levels of 2-AG and higher CSF levels of AEA compared to healthy controls (Mann-Whitney statistics = 303.0, p = 0.02). Patients with PD without LID had lower CSF levels of 2-AG (Kruskal-Wallis statistics = 7.76, p = 0.02) and higher CSF levels of AEA levels than healthy controls (Kruskal-Wallis statistics = 8.81, p = 0.01). The findings suggest that the endocannabinoid system participates in the pathophysiology of PD symptoms, but its role in the pathophysiology of LID is still unclear.
左旋多巴诱导的运动障碍(LID)是帕金森病(PD)的常见并发症,而内源性大麻素系统在其病理生理学中起作用。通过测量有和没有 LID 的 PD 患者以及健康对照者的血浆和 CSF 中 α-N-花生四烯酸乙醇胺(AEA)和 2-花生四烯酰甘油(2-AG)的水平,来检验内源性大麻素系统在 PD 和 LID 中的功能会改变的假设。从 20 名健康对照者、23 名无 LID 的 PD 患者和 24 名有 LID 的 PD 患者中采集血液和 CSF 样本。使用高度敏感的柱切换超高效液相色谱-串联质谱法测量 AEA 和 2-AG 的水平。当汇总在一起时,与健康对照组相比,PD 患者的血浆和 CSF 中的 2-AG 水平较低,而 CSF 中的 AEA 水平较高(Mann-Whitney 统计量 = 303.0,p = 0.02)。无 LID 的 PD 患者的 CSF 中 2-AG 水平较低(Kruskal-Wallis 统计量 = 7.76,p = 0.02),而 CSF 中的 AEA 水平高于健康对照组(Kruskal-Wallis 统计量 = 8.81,p = 0.01)。这些发现表明,内源性大麻素系统参与 PD 症状的病理生理学,但它在 LID 的病理生理学中的作用仍不清楚。