中枢单胺类神经递质在酒精依赖中的分子作用机制  

Alcohol dependence mediated by monoamine neurotransmitters in the central nervous system

作　　者：杨晓华[1] 张华峰[2] 赖江华[1] 

机构地区：[1]西安交通大学医学院,卫生部法医学重点实验室,西安710061 [2]陕西师范大学食品工程与营养科学学院,西安710062

出　　处：《遗传》2014年第1期11-20,共10页Hereditas（Beijing)

基　　金：国家自然科学基金项目(编号:81373247);中央高校基本科研业务费专项资金项目(编号:GK201302048)资助

摘　　要：酒精依赖是以失去控制地饮用酒精为特征的慢性、复发性脑疾病,业已成为严重的社会问题。中枢单胺类神经递质(包括多巴胺、5-羟色胺等)在酒精依赖症的发生、发展和系统功能失调中发挥着重要作用。文章探讨了单胺类神经递质关键调控点多巴胺受体、5-羟色胺受体、转运体、酪氨酸羟化酶、色氨酸羟化酶及单胺氧化酶基因等在酒精依赖中的作用机制,结合本实验室在基因敲除小鼠模型方面的研究进展提出了酒精依赖分子机制的研究策略。在系统评述中枢单胺类神经递质介导的酒精依赖分子作用机制的基础上,结合本实验室在酪氨酸羟化酶激活剂钙调蛋白依赖的蛋白激酶Ⅱ方面的研究成果探讨了可用于酒精依赖症治疗的作用靶点,提出通过调整基因调控区的甲基化程度和改变pre-mRNA的选择性剪切等表观遗传学策略预防和治疗酒精依赖症,同时根据基因多态性研究结果提出对酒精依赖症患者进行个性化预防和治疗的新策略。Alcohol dependence, a chronic relapsing brain disease with the characteristics of drinking alcohol out of con trol, has become a serious social problem. Monoamine neurotransmitters, mainly including dopamine and 5-hydroxytryp tamine, play important roles in the occurrence, development and neural dysfunction of alcohol dependence syndrome. In this review, the roles of key factors of the monoamine system （dopamine receptor genes, 5-hydroxytryptamine receptor genes, transporter genes, tyrosine hydroxylase gene, tryptophanhydroxylase gene and monoamine oxidase gene） in alcohol dependence were discussed, and strategies for further studies of molecular mechanisms were proposed based on gene knockout mice models generated in our laboratory. Then, combining with studies on tyrosine hydroxylase activator CaMKIIin our lab, therapeutic targets were discussed. Besides, epigenetic strategies for prevention and treatment of alcohol de pendence syndrome were proposed. Furthermore, manipulating methylation levels in gene regulatory regions and alterna tive splicing of pre-mRNAs might also have clinical implications. Finally, based on new findings on genetic polymorphism, it is of great potential to carry out individual prevention and treatment for patients suffering from alcohol dependence.

关 键 词：酒精依赖 单胺类神经递质 分子作用机制 治疗靶点 

分 类 号：R749.62[医药卫生—神经病学与精神病学]