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酒精依赖与编码α2和γ1 GABAA受体亚基的基因:来自人类和小鼠的见解

Alcohol Dependence and Genes Encoding α2 and γ1 GABAA Receptor Subunits: Insights from Humans and Mice.

作者信息

Borghese Cecilia M, Harris R Adron

机构信息

Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, Texas.

出版信息

Alcohol Res. 2012;34(3):345-53.

Abstract

One approach to identifying the causes of alcoholism, particularly without crossing ethical boundaries in human subjects, is to look at the person's genome (and particularly at the variations that naturally arise in the DNA) to identify those variations that seem to be found more commonly in people with the disease. Some of these analyses have focused on the genes that encode subunits of the receptor for the brain chemical (i.e., neurotransmitter) γ-aminobutyric acid (GABA). Different epidemiological genetic studies have provided evidence that variations in certain GABAA receptor (GABAA-R) subunits, particularly subunits α2 and γ1, are correlated with alcohol dependence. Manipulations of these genes and their expression in mice and rats also are offering clues as to the role of specific GABAA-Rs in the molecular mechanisms underlying alcoholism and suggest possibilities for new therapeutic approaches.

摘要

一种识别酒精中毒原因的方法,特别是在不跨越人体受试者伦理界限的情况下,是研究人的基因组(尤其是DNA中自然出现的变异),以识别那些似乎在患有该疾病的人群中更常见的变异。其中一些分析聚焦于编码大脑化学物质(即神经递质)γ-氨基丁酸(GABA)受体亚基的基因。不同的流行病学基因研究提供了证据,表明某些GABAA受体(GABAA-R)亚基的变异,特别是α2和γ1亚基,与酒精依赖有关。对这些基因及其在小鼠和大鼠体内表达的操控,也为特定GABAA-R在酒精中毒潜在分子机制中的作用提供了线索,并为新的治疗方法带来了可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da0/3860398/44f800b5bbdd/arcr-34-3-345f2.jpg

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