Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, UNSW Sydney, NSW, 2052, Australia.
Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, UNSW Sydney, NSW, 2052, Australia.
Neuropharmacology. 2021 Jun 1;190:108555. doi: 10.1016/j.neuropharm.2021.108555. Epub 2021 Apr 9.
Recent years have yielded significant advances in our understanding of microglia, the immune cells of the central nervous system (CNS). Microglia are key players in CNS development, immune surveillance, and the maintenance of proper neuronal function throughout life. In the healthy brain, homeostatic microglia have a unique molecular signature. In neurological diseases, microglia become activated and adopt distinct transcriptomic signatures, including disease-associated microglia (DAM) implicated in neurodegenerative disorders. Homeostatic microglia synthesise the endogenous cannabinoids 2-arachidonoylglycerol and anandamide and express the cannabinoid receptors CB1 and CB2 at constitutively low levels. Upon activation, microglia significantly increase their synthesis of endocannabinoids and upregulate their expression of CB2 receptors, which promote a protective microglial phenotype by enhancing their production of neuroprotective factors and reducing their production of pro-inflammatory factors. Here, we summarise the effects of the microglial cannabinoid system in the CNS demyelinating disease multiple sclerosis, the neurodegenerative diseases Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, chronic inflammatory and neuropathic pain, and psychiatric disorders including depression, anxiety and schizophrenia. We discuss the therapeutic potential of cannabinoids in regulating microglial activity and highlight the need to further investigate their specific microglia-dependent immunomodulatory effects.
近年来，我们对中枢神经系统（CNS）中的免疫细胞——小胶质细胞的理解取得了重大进展。小胶质细胞是 CNS 发育、免疫监视以及维持整个生命周期适当神经元功能的关键参与者。在健康的大脑中，稳态小胶质细胞具有独特的分子特征。在神经疾病中，小胶质细胞被激活并呈现出独特的转录组特征，包括与神经退行性疾病相关的小胶质细胞（DAM）。稳态小胶质细胞合成内源性大麻素 2-花生四烯酸甘油和大麻素，以低水平组成型表达大麻素受体 CB1 和 CB2。在激活后，小胶质细胞显著增加内源性大麻素的合成，并上调 CB2 受体的表达，通过增强其神经保护因子的产生和减少促炎因子的产生，促进保护性小胶质细胞表型。在这里，我们总结了小胶质细胞大麻素系统在中枢神经系统脱髓鞘疾病多发性硬化症、神经退行性疾病阿尔茨海默病、帕金森病和肌萎缩侧索硬化症、慢性炎症和神经病理性疼痛以及包括抑郁症、焦虑症和精神分裂症在内的精神疾病中的作用。我们讨论了大麻素在调节小胶质细胞活性方面的治疗潜力，并强调需要进一步研究它们对特定小胶质细胞依赖的免疫调节作用。
