The University of Texas at Austin, College of Pharmacy, Division of Pharmacology & Toxicology, Austin, TX, United States.
University of Kentucky, College of Pharmacy, Department of Pharmaceutical Sciences, Lexington, KY, United States.
Prog Mol Biol Transl Sci. 2019;167:179-221. doi: 10.1016/bs.pmbts.2019.06.011. Epub 2019 Jul 29.
Alcohol use disorder (AUD) is a chronic relapsing disorder with wide-ranging health consequences. Alcohol targets the central nervous system producing neurodegeneration and subsequent cognitive and behavioral deficits, but the mechanisms behind these effects remain unclear. Recently, evidence has been mounting for the role of neuroimmune activation in the pathogenesis of AUDs, but our nascent state of knowledge about the interaction of alcohol with the neuroimmune system supports that the relationship is complicated. As the resident macrophage of the central nervous system, microglia are a central focus. Human and animal research on the interplay between microglia and alcohol in AUDs has proven to be complex, and though early research focused on a pro-inflammatory phenotype of microglia, the anti-inflammatory and homeostatic roles of microglia must be considered. How these new roles for microglia should be incorporated into our thinking about the neuroimmune system in AUDs is discussed in the context of developing novel pharmacotherapies for AUDs.
酒精使用障碍(AUD)是一种慢性复发性疾病,会对健康造成广泛影响。酒精会对中枢神经系统产生影响,导致神经退行性变和随后的认知及行为缺陷,但这些影响的机制仍不清楚。最近,越来越多的证据表明神经免疫激活在 AUD 发病机制中的作用,但我们对酒精与神经免疫系统相互作用的认识还处于起步阶段,这表明这种关系很复杂。小胶质细胞作为中枢神经系统的常驻巨噬细胞,是一个核心关注点。在 AUD 中,人类和动物研究已经证明小胶质细胞与酒精之间的相互作用非常复杂,尽管早期的研究集中在小胶质细胞的促炎表型上,但必须考虑小胶质细胞的抗炎和稳态作用。在讨论开发 AUD 新型药物治疗的背景下,本文讨论了如何将小胶质细胞的这些新作用纳入我们对 AUD 中神经免疫系统的思考。