Kim Hee-Dae, Call Tanessa, Magazu Samantha, Ferguson Deveroux
Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, 85004, USA.
Adv Exp Med Biol. 2017;978:127-143. doi: 10.1007/978-3-319-53889-1_7.
Acute and prolonged exposure to drugs of abuse induces changes in gene expression, synaptic function, and neural plasticity in brain regions involved in reward. Numerous genes are involved in this process, and persistent changes in gene expression coincide with epigenetic histone modifications and DNA methylation. Histone modifications are attractive regulatory mechanisms, which can encode complex environmental signals in the genome of postmitotic cells, like neurons. Recently, it has been demonstrated that specific histone modifications are involved in addiction-related gene regulatory mechanisms, by a diverse set of histone-modifying enzymes and readers. These histone modifiers and readers may prove to be valuable pharmacological targets for effective treatments for drug addiction.
急性和长期接触滥用药物会导致参与奖赏的脑区基因表达、突触功能和神经可塑性发生变化。许多基因参与这一过程,基因表达的持续变化与表观遗传组蛋白修饰和DNA甲基化相一致。组蛋白修饰是有吸引力的调控机制,其可以在有丝分裂后细胞(如神经元)的基因组中编码复杂的环境信号。最近,已经证明特定的组蛋白修饰通过多种组蛋白修饰酶和读取器参与成瘾相关的基因调控机制。这些组蛋白修饰因子和读取器可能被证明是有效治疗药物成瘾的有价值的药理学靶点。