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表观遗传修饰、酒精性脑损伤与潜在药物靶点

Epigenetic Modifications, Alcoholic Brain and Potential Drug Targets.

作者信息

Jangra Ashok, Sriram Chandra Shaker, Pandey Suryanarayan, Choubey Priyansha, Rajput Prabha, Saroha Babita, Bezbaruah Babul Kumar, Lahkar Mangala

机构信息

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, India.

Department of Biotechnology, University Institute of Engineering and Technology (UIET), Maharshi Dayanand University, Rohtak, India.

出版信息

Ann Neurosci. 2016 Oct;23(4):246-260. doi: 10.1159/000449486. Epub 2016 Oct 4.

Abstract

Acute and chronic alcohol exposure evidently influences epigenetic changes, both transiently and permanently, and these changes in turn influence a variety of cells and organ systems throughout the body. Many of the alcohol-induced epigenetic modifications can contribute to cellular adaptations that ultimately lead to behavioral tolerance and alcohol dependence. The persistence of behavioral changes demonstrates that long-lasting changes in gene expression, within particular regions of the brain, may contribute importantly to the addiction phenotype. The research activities over the past years have demonstrated a crucial role of epigenetic mechanisms in causing long lasting and transient changes in the expression of several genes in diverse tissues, including brain. This has stimulated recent research work that is aimed at characterizing the influence of epigenetic regulatory events in mediating the long lasting and transient effects of alcohol abuse on the brain in humans and animal models of alcohol addiction. In this study, we update our current understanding of the impact of alcohol exposure on epigenetic mechanisms in the brain and refurbish the knowledge of epigenetics in the direction of new drugs development.

摘要

急性和慢性酒精暴露显然会对表观遗传变化产生影响,这种影响既有短暂的,也有永久性的,而这些变化反过来又会影响全身的各种细胞和器官系统。许多酒精诱导的表观遗传修饰可导致细胞适应性变化,最终导致行为耐受性和酒精依赖。行为变化的持续性表明,大脑特定区域内基因表达的长期变化可能对成瘾表型起着重要作用。过去几年的研究活动表明,表观遗传机制在导致包括大脑在内的多种组织中多个基因表达的长期和短暂变化方面起着关键作用。这激发了近期的研究工作,旨在描述表观遗传调控事件在介导酒精滥用对人类和酒精成瘾动物模型大脑的长期和短暂影响中的作用。在本研究中,我们更新了目前对酒精暴露对大脑表观遗传机制影响的理解,并朝着新药开发的方向完善了表观遗传学知识。

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