Proteomic analysis of the nucleus accumbens in rhesus monkeys of morphine dependence and withdrawal intervention
Proteomic analysis of the nucleus accumbens in rhesus monkeys of morphine dependence and withdrawal intervention
复制标题
吗啡依赖和戒断干预恒河猴伏核的蛋白质组学分析。
DOI：
10.1016/j.jprot.2011.11.008
复制
发表时间：
2012-02-02
影响因子：
3.3
通讯作者：
Cen, Xiaobo
中科院分区：
文献类型：
--
作者：
Bu, Qian;Yang, Yanzhu;Cen, Xiaobo
已知吗啡的强化作用和长期后果与大脑中的中脑边缘多巴胺通路的关键区域--丘脑核（NAc）密切相关。然而，参与吗啡依赖灵长类动物神经适应过程和戒断症状的蛋白质还没有得到很好的研究。在本研究中，我们对吗啡依赖和可乐定或美沙酮戒断干预的恒河猴NAc进行了蛋白质组学研究。双向电泳用于比较NAc中胞浆蛋白丰度的变化。共发现46个差异表达蛋白，并通过质谱分析进一步鉴定。已鉴定的蛋白质可分为6类：代谢和线粒体功能、突触传递、细胞骨架蛋白、氧化应激、信号转导和蛋白质合成与降解。重要的是，我们发现14种蛋白质在可乐定或美沙酮戒断治疗后发生了显著但相似的改变，揭示了治疗吗啡成瘾的潜在药理学策略或靶点。本研究为深入了解灵长类动物吗啡成瘾和戒断治疗的神经病理生理机制提供了新的思路，有助于阿片类药物戒断治疗的发展。(C)2011 Elsevier B. V.保留所有权利。
It has been known that the reinforcing effects and long-term consequences of morphine are closely associated with nucleus accumbens (NAc) in the brain, a key region of the mesolimbic dopamine pathway. However, the proteins involved in neuroadaptive processes and withdrawal symptom in primates of morphine dependence have not been well explored. In the present study, we performed proteomes in the NAc of rhesus monkeys of morphine dependence and withdrawal intervention with clonidine or methadone. Two-dimensional electrophoresis was used to compare changes in cytosolic protein abundance in the NAc. We found a total of 46 proteins differentially expressed, which were further identified by mass spectrometry analysis. The identified proteins can be classified into 6 classes: metabolism and mitochondrial function, synaptic transmission, cytoskeletal proteins, oxidative stress, signal transduction and protein synthesis and degradation. Importantly, we discovered 14 proteins were significantly but similarly altered after withdrawal therapy with clonidine or methadone, revealing potential pharmacological strategies or targets for the treatment of morphine addiction. Our study provides a comprehensive understanding of the neuropathophysiology associated with morphine addiction and withdrawal therapy in primate, which is helpful for the development of opiate withdrawal pharmacotherapies. (C) 2011 Elsevier B.V. All rights reserved.