专题：Science报道
据1月8日的《科学》杂志报道说，在一项有助于解释药物成瘾的生物学基础的小鼠研究中，科研人员显示了可卡因是如何影响某些与伏核中基因的开与关有关的系统的。
伏核是脑中“奖励”回路中的一个关键性的中心。 人们已知可卡因成瘾会造成该环路中基因表达的持久性变化，以及其适应新环境的能力，而这些变化可能是可卡因成瘾的某些行为效应的基础。
Ian Maze及其同僚在小鼠中分析了某些发生在脑神经元染色体中的分子相互作用，这些相互作用最终影响了不同基因的表达。 他们发现，长期接触可卡因会导致某些形式的“组蛋白赖氨酸甲基化”的减少，这是伏核中染色体部分的一种生物化学性修饰。 这种组蛋白赖氨酸甲基化减少可增加某些神经元的可塑性，使得它们变得异常容易进行相互连接，而且还会增加小鼠对可卡因的偏好。
研究人员说，更好地理解通过这些过程而受到调节的基因可帮助研发出更为有效的成瘾性疾病的治疗方法。
推荐原始出处：
Science 8 January 2010: DOI: 10.1126/science.1179438
Essential Role of the Histone Methyltransferase G9a in Cocaine-Induced Plasticity
Ian Maze,1 Herbert E. Covington, III,1 David M. Dietz,1 Quincey LaPlant,1,2 William Renthal,2 Scott J. Russo,1 Max Mechanic,2 Ezekiell Mouzon,1 Rachael L. Neve,3 Stephen J. Haggarty,4,5 Yanhua Ren,1 Srihari C. Sampath,6 Yasmin L. Hurd,1 Paul Greengard,7 Alexander Tarakhovsky,6 Anne Schaefer,7 Eric J. Nestler1,*
Cocaine-induced alterations in gene expression cause changes in neuronal morphology and behavior that may underlie cocaine addiction. In mice, we identified an essential role for histone 3 lysine 9 (H3K9) dimethylation and the lysine dimethyltransferase G9a in cocaine-induced structural and behavioral plasticity. Repeated cocaine administration reduced global levels of H3K9 dimethylation in the nucleus accumbens. This reduction in histone methylation was mediated through the repression of G9a in this brain region, which was regulated by the cocaine-induced transcription factor FosB. Using conditional mutagenesis and viral-mediated gene transfer, we found that G9a down-regulation increased the dendritic spine plasticity of nucleus accumbens neurons and enhanced the preference for cocaine, thereby establishing a crucial role for histone methylation in the long-term actions of cocaine.
1 Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA.
2 Departments of Psychiatry and Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
3 Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
4 Psychiatric and Neurodevelopmental Genetics Unit and Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
5 Stanley Center for Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
6 Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, NY, USA.
7 Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA.
