Epigenetic mechanisms of drug addiction.
Epigenetic mechanisms of drug addiction.
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DOI：
10.1016/j.neuropharm.2013.04.004
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发表时间：
2014-01
影响因子：
4.7
通讯作者：
Nestler EJ
中科院分区：
文献类型：
--
作者：
Nestler EJ
药物成瘾涉及潜在的终身行为异常，这些行为异常是由于反复暴露于滥用药物而导致的。这些行为变化的持续性表明，大脑特定区域内基因表达的长期变化可能对成瘾表型有重要贡献。过去十年的工作已经证明了表观遗传机制在驱动包括大脑在内的各种组织中基因表达的持久变化方面的关键作用。这促使最近的研究，旨在表征影响的表观遗传调控事件介导的持久影响药物滥用对大脑的药物成瘾的动物模型。本次审查提供了一个进展报告，这仍然是早期的工作在外地。正如我们将看到的，有强有力的证据表明，反复暴露于滥用药物诱导大脑的奖励区域内的变化，在三个主要模式的表观遗传调节组蛋白修饰，如乙酰化和甲基化，DNA甲基化，和非编码RNA。在一些情况下，已经有可能直接证明这种表观遗传变化对成瘾相关行为异常的贡献。对成瘾的表观遗传机制的研究也提供了一个前所未有的观点，即受重复药物暴露影响的基因和非基因区域的范围以及这种调节的精确分子基础。现在需要验证这项工作在人类成瘾中的关键方面，并评估挖掘这些信息以开发新的诊断测试和更有效的成瘾综合征治疗方法的可能性。
Drug addiction involves potentially life-long behavioral abnormalities that are caused in vulnerable individuals by repeated exposure to a drug of abuse. The persistence of these behavioral changes suggests that long-lasting changes in gene expression, within particular regions of the brain, may contribute importantly to the addiction phenotype. Work over the past decade has demonstrated a crucial role for epigenetic mechanisms in driving lasting changes in gene expression in diverse tissues, including brain. This has prompted recent research aimed at characterizing the influence of epigenetic regulatory events in mediating the lasting effects of drugs of abuse on the brain in animal models of drug addiction. This review provides a progress report of this still early work in the field. As will be seen, there is robust evidence that repeated exposure to drugs of abuse induces changes within the brain’s reward regions in three major modes of epigenetic regulation—histone modifications such as acetylation and methylation, DNA methylation, and non-coding RNAs. In several instances, it has been possible to demonstrate directly the contribution of such epigenetic changes to addiction-related behavioral abnormalities. Studies of epigenetic mechanisms of addiction are also providing an unprecedented view of the range of genes and non-genic regions that are affected by repeated drug exposure and the precise molecular basis of that regulation. Work is now needed to validate key aspects of this work in human addiction and evaluate the possibility of mining this information to develop new diagnostic tests and more effective treatments for addiction syndromes.
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