中枢单胺类神经递质在酒精依赖中的分子作用机制

doi:10.3724/SP.J.1005.2014.00011

遗传 ›› 2014, Vol. 36 ›› Issue (1): 11-20.doi: 10.3724/SP.J.1005.2014.00011

中枢单胺类神经递质在酒精依赖中的分子作用机制

杨晓华¹, 张华峰², 赖江华¹

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

收稿日期:2013-08-22 修回日期:2013-10-19 出版日期:2014-01-20 发布日期:2013-12-20
通讯作者: 赖江华, 教授, 博士生导师, 研究方向：基因组多态性与毒品依赖分子机制。 E-mail:laijh1011@mail.xjtu.edu.cn
作者简介:杨晓华, 博士研究生, 专业方向：分子细胞生物学。Tel: 029-82657505; E-mail: xhyang@mail.xjtu.edu.cn
基金资助:
国家自然科学基金项目(编号：81373247)与中央高校基本科研业务费专项资金项目(编号：GK201302048)资助

Alcohol dependence mediated by monoamine neurotransmitters in the central nervous system

Xiaohua Yang¹, Huafeng Zhang², Jianghua Lai¹

1. Key Laboratory of Ministry of Health for Forensic Sciences, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, China;
2. College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an 710062, China

Received:2013-08-22 Revised:2013-10-19 Online:2014-01-20 Published:2013-12-20

摘要/Abstract

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。

关键词: 酒精依赖, 单胺类神经递质, 分子作用机制, 治疗靶点

Abstract:

Alcohol dependence, a chronic relapsing brain disease with the characteristics of drinking alcohol out of control, 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 CaMKII in our lab, therapeutic targets were discussed. Besides, epigenetic strategies for prevention and treatment of alcohol dependence syndrome were proposed. Furthermore, manipulating methylation levels in gene regulatory regions and alternative 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.

Key words: alcohol dependence, monoamine neurotransmitter, molecular mechanism, therapeutic target

杨晓华, 张华峰, 赖江华. 中枢单胺类神经递质在酒精依赖中的分子作用机制[J]. 遗传, 2014, 36(1): 11-20.

Xiaohua Yang, Huafeng Zhang, Jianghua Lai. Alcohol dependence mediated by monoamine neurotransmitters in the central nervous system[J]. HEREDITAS, 2014, 36(1): 11-20.

参考文献

[1] Tang YL, Xiang XJ, Wang XY, Cubells JF, Babor TF, Hao W. Alcohol and alcohol-related harm in China: policy changes needed. Bull World Health Organ, 2013, 91(4): 270–276. <\p>

[2] 李菁, 袁孝如. 酒精依赖大鼠皮质CREB变化及氟西汀对其影响. 中国药理学通报, 2003, 19(2): 163–167. <\p>

[3] Hao W, Chen HH, Su ZH. China: alcohol today. Addiction, 2005, 100(6): 737–741. <\p>

[4] Anderson PD, Bokor G. Forensic aspects of drug–induced violence. J Pharm Pract, 2012, 25(1): 41–49. <\p>

[5] Laramée P, Kusel J, Leonard S, Aubin HJ, François C, Daeppen JB. The economic burden of alcohol dependence in Europe. Alcohol Alcohol, 2013, 48(3): 259–269. <\p>

[6] 陈乃宏. 神经递质与神经疾患. 北京: 中国协和医科大学出版社, 2012: 185–243. <\p>

[7] Garwood P, Lanfumey L, Hamon M. Alcohol dependence and polymorphisms of serotonin-related genes. Med Sci (Paris), 2004, 20(12): 1132–1138. <\p>

[8] 李凡, 舒斯云, 包新民. 多巴胺受体的结构和功能. 中国神经科学杂志, 2003, 19(6): 405–410. <\p>

[9] 李生斌, 朱永生. 冲动与多巴胺系统在毒品依赖中的作用机制. 西安交通大学学报(医学版), 2012, 33(1): 1–4. <\p>

[10] 韦丰, 周儒伦, 沈渔邨, 田成华, 郑晓华, 赵惠丽, 李延知, 彭华, 范建华, 周朝凤. 多巴胺D2受体基因的一种短串联重复多态性与汉族酒依赖相关的家系对照研究. 中国神经科学杂志, 1999, 15(1): 13–16. <\p>

[11] Mignini F, Napolioni V, Codazzo C, Carpi FM, Vitali M, Romeo M, Ceccanti M. DRD2/ANKK1 Taq1A and SLC6A3 VNTR polymorphisms in alcohol dependence: association and gene-gene interaction study in a population of Central Italy. Neurosci Lett, 2012, 522(2): 103–107. <\p>

[12] van der Zwaluw CS, Kuntsche E, Engels RCME. Risky alcohol use in adolescence: the role of genetics (DRD2, SLC6A4) and coping motives. Alcohol Clin Exp Res, 2011, 35(4): 756–764. <\p>

[13] Kazantseva A, Gaysina D, Malykh S, Khusnutdinova E. The role of dopamine transporter (SLC6A3) and dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) gene polymorphisms in personality traits. Prog Neuropsychopharmacol Biol Psychiatry, 2011, 35(4): 1033–1040. <\p>

[14] Suraj SH, Ghosh PK, Saraswathy KN. DRD2 and ANKK1 gene polymorphisms and alcohol dependence: a case-control study among a Mendelian population of East Asian ancestry. Alcohol Alcohol, 2013, 48(4): 409–414. <\p>

[15] Lee SH, Lee BH, Lee JS, Chai YG, Choi MR, Han DMR, Ji H, Jang GH, Shin HE, Choi IG. The association of DRD2-141C and ANKK1 TaqIA polymorphisms with alcohol dependence in Korean population classified by the Lesch Typology. Alcohol Alcohol, 2013, 48(4): 426–432. <\p>

[16] Swagell CD, Lawford BR, Hughes IP, Voisey J, Feeney GFX, van Daal A, Connor JP, Noble EP, Morris CP, Young RM. DRD2 C957T and TaqIA genotyping reveals gender effects and unique low-risk and high-risk genotypes in alcohol dependence. Alcohol Alcohol, 2012, 47(4): 397–403. <\p>

[17] 武晓华, 钟树荣, 高长青, 鲍建军, 胡利平, 阮冶, 景强. 酒精依赖综合征患者DRD2、DRD4和DAT基因多态性的研究. 现代生物医学进展, 2009, 9(8): 1440–1442, 1468. <\p>

[18] Kitis A, Akvardar Y, Eresen C, Kizildag S, Akpulat U, Yildirimcan S, Alptekin K, Akdede BB, Arkar H. The role of dopamine 2 receptor gene and personality characteristics in alcohol dependence in Turkish population. Eur Neuropsychopharmacol, 2006, 16(4): S491. <\p>

[19] Prasad P, Ambekar A, Vaswani M. Dopamine D2 receptor polymorphisms and susceptibility to alcohol dependence in Indian males: a preliminary study. BMC Med Genet, 2010, 11(2): 24. <\p>

[20] Meyers JL, Nyman E, Loukola A, Rose RJ, Kaprio J, Dick DM. The association between DRD2/ANKK1 and genetically informed measures of alcohol use and problems. Addict Biol, 2013, 18(3): 523–536. <\p>

[21] 龙海英, 范华, 张燕敏, 王茜, 巩凤芹, 张付全. DRD2基因C957T多态性与中国汉族精神分裂症的相关性. 中国现代医学杂志, 2010, 20(10): 1474–1476, 1481. <\p>

[22] Arinami T, Gao M, Hamaguchi H, Toru M. A functional polymorphism in t

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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

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