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表观遗传机制在酒精成瘾中的新作用

Emerging Role of Epigenetic Mechanisms in Alcohol Addiction.

作者信息

Berkel Tiffani D M, Pandey Subhash C

机构信息

Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois.

Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois.

出版信息

Alcohol Clin Exp Res. 2017 Apr;41(4):666-680. doi: 10.1111/acer.13338. Epub 2017 Feb 18.

Abstract

Alcohol use disorder (AUD) is a complex brain disorder with an array of persistent behavioral and neurochemical manifestations. Both genetic and environmental factors are known to contribute to the development of AUD, and recent studies on alcohol exposure and subsequent changes in gene expression suggest the importance of epigenetic mechanisms. In particular, histone modifications and DNA methylation have emerged as important regulators of gene expression and associated phenotypes of AUD. Given the therapeutic potential of epigenetic targets, this review aims to summarize the role of epigenetic regulation in our current understanding of AUD by evaluating known epigenetic signatures of brain regions critical to addictive behaviors in both animal and human studies throughout various stages of AUD. More specifically, the effects of acute and chronic alcohol exposure, tolerance, and postexposure withdrawal on epigenetically induced changes to gene expression and synaptic plasticity within key brain regions and the associated behavioral phenotypes have been discussed. Understanding the contribution of epigenetic regulation to crucial signaling pathways may prove vital for future development of novel biomarkers and treatment agents in ameliorating or preventing AUD.

摘要

酒精使用障碍(AUD)是一种复杂的脑部疾病,具有一系列持续的行为和神经化学表现。已知遗传和环境因素都对AUD的发展有影响,最近关于酒精暴露和随后基因表达变化的研究表明表观遗传机制的重要性。特别是,组蛋白修饰和DNA甲基化已成为AUD基因表达及相关表型的重要调节因子。鉴于表观遗传靶点的治疗潜力,本综述旨在通过评估在AUD各个阶段的动物和人类研究中,对成瘾行为至关重要的脑区已知的表观遗传特征,总结表观遗传调控在我们当前对AUD的理解中的作用。更具体地说,已经讨论了急性和慢性酒精暴露、耐受性以及暴露后戒断对关键脑区内基因表达和突触可塑性的表观遗传诱导变化以及相关行为表型的影响。了解表观遗传调控对关键信号通路的贡献,可能对未来开发用于改善或预防AUD的新型生物标志物和治疗药物至关重要。

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