Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, United States.
Neurobiol Learn Mem. 2011 Jul;96(1):53-60. doi: 10.1016/j.nlm.2011.02.015. Epub 2011 Mar 8.
The role of epigenetic mechanisms in control of gene expression during mammalian development is well established. Associations between specific DNA or histone modifications and numerous neurodevelopmental and neurodegenerative disorders implies significant consequences of epigenetic dysregulation in both the developing and mature brain, the latter of which is the general focus of this review. Accumulating evidence suggests that epigenetic changes are involved in normal cognitive processes in addition to neurological and psychiatric disorders. Recent investigations into the regulation of epigenetic modifications in the adult brain have revealed novel and surprisingly dynamic mechanisms for controlling learning and memory-related behaviors as well as long-term synaptic plasticity. DNA methylation and histone acetylation have also been implicated in the modulation of basal synaptic transmission and the balance between excitation and inhibition in various brain regions. Studies have begun to uncover some of the alterations in gene expression that appear to mediate many of these effects, but an understanding of the precise mechanisms involved is still lacking. Nevertheless, the fundamental importance of epigenetic processes in influencing neuronal activity is becoming increasingly evident.
在哺乳动物发育过程中,表观遗传机制在控制基因表达方面的作用已得到充分证实。特定的 DNA 或组蛋白修饰与许多神经发育和神经退行性疾病之间的关联表明,表观遗传失调对发育中和成熟的大脑都有重大影响,后者是本综述的一般重点。越来越多的证据表明,表观遗传变化除了与神经和精神疾病有关外,还与正常认知过程有关。最近对成年人大脑表观遗传修饰调控的研究揭示了控制学习和记忆相关行为以及长期突触可塑性的新的、令人惊讶的动态机制。DNA 甲基化和组蛋白乙酰化也被认为参与了调节不同脑区的基础突触传递和兴奋与抑制之间的平衡。研究已经开始揭示一些似乎介导许多这些效应的基因表达改变,但对涉及的确切机制仍知之甚少。然而,表观遗传过程在影响神经元活动方面的重要性正变得越来越明显。