Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.
Department of Drug Design and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Brain Res Bull. 2022 Jan;178:82-96. doi: 10.1016/j.brainresbull.2021.11.009. Epub 2021 Nov 20.
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic (DAergic) neurons of the substantia nigra pars compacta (SNc) by neurodegeneration. Recent findings in animal models of PD propose tonic inhibition of the remaining DA neurons through GABA release from reactive glial cells. Movement dysfunctions could be ameliorated by promotion of activity in dormant DA cells. The endocannabinoid system (ECS) is extensively present in basal ganglia (BG) and is known as an indirect modulator of DAergic neurotransmission, thus drugs designed to target this system have shown promising therapeutic potential in PD patients. Interestingly, down/up-regulation of cannabinoid receptors (CBRs) varies across the different stages of PD, suggesting that some of the motor/ non-motor deficits may be related to changes in CBRs. Determination of the profile of changes of these receptors across the different stages of PD as well as their neural distribution within the BG could improve understanding of PD and identify pathways important in disease pathobiology. In this review, we focus on temporal and spatial alterations of CBRs during PD in the BG. At present, as inconclusive, but suggestive results have been obtained, future investigations should be conducted to extend preclinical studies examining CBRs changes within each stage in controlled clinical trials in order to determine the potential of targeting CBRs in management of PD.
帕金森病（PD）的特征是神经退行性变导致黑质致密部（SNc）的多巴胺能（DAergic）神经元进行性丧失。PD 动物模型的最新研究结果表明，反应性神经胶质细胞释放 GABA 会对剩余的 DA 神经元产生紧张性抑制。通过促进休眠 DA 细胞的活性，可以改善运动功能障碍。内源性大麻素系统（ECS）广泛存在于基底神经节（BG）中，作为 DA 能神经传递的间接调节剂，因此，针对该系统的药物在 PD 患者中显示出有希望的治疗潜力。有趣的是，大麻素受体（CBRs）的下调/上调在 PD 的不同阶段有所不同，这表明一些运动/非运动缺陷可能与 CBRs 的变化有关。确定这些受体在 PD 的不同阶段的变化情况及其在 BG 中的神经分布，可以增进对 PD 的了解，并确定疾病病理生物学中的重要途径。在这篇综述中，我们重点介绍了 PD 期间 BG 中 CBRs 的时空变化。目前，虽然得到的结果不确定，但提示性结果已经得出，未来的研究应该在对照临床试验中进行，以扩展每个阶段的 CBRs 变化的临床前研究，以确定针对 CBRs 管理 PD 的潜力。
