神经免疫信号：酒精滥用的关键组成部分。
Neuroimmune signaling: a key component of alcohol abuse.
机构信息
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, TX 78712, USA.
出版信息
Curr Opin Neurobiol. 2013 Aug;23(4):513-20. doi: 10.1016/j.conb.2013.01.024. Epub 2013 Feb 22.
Abstract
Molecular and behavioral studies corroborate a pivotal role for the innate immune system in mediating the acute and chronic effects of alcohol and support a neuroimmune hypothesis of alcohol addiction. Changes in expression of neuroimmune genes and microglial transcripts occur in postmortem brain from alcoholics and animals exposed to alcohol, and null mutant animals lacking certain innate immune genes show decreased alcohol-mediated responses. Many of the differentially expressed genes are part of the toll like receptor (TLR) signaling pathway and culminate in an increased expression of pro-inflammatory immune genes. Compounds known to inhibit inflammation, microglial activation, and neuroimmune gene expression have shown promising results in reducing alcohol-mediated behaviors in animal models, indicating that neuroimmune signaling pathways offer unexplored targets in the treatment of alcohol abuse.
摘要
分子和行为研究证实，先天免疫系统在介导酒精的急性和慢性效应方面起着关键作用，并支持酒精成瘾的神经免疫假说。酒精中毒者和暴露于酒精的动物的死后大脑中，神经免疫基因和小胶质细胞转录本的表达发生变化，而缺乏某些先天免疫基因的缺失突变动物表现出酒精介导反应减少。许多差异表达的基因是 toll 样受体 (TLR) 信号通路的一部分，最终导致促炎免疫基因的表达增加。已知可抑制炎症、小胶质细胞激活和神经免疫基因表达的化合物在减少动物模型中的酒精介导行为方面显示出有希望的结果，这表明神经免疫信号通路为治疗酒精滥用提供了未开发的靶点。
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