Kennedy Andrew J, Sweatt J David
a Department of Neurobiology , University of Alabama at Birmingham , Birmingham , AL , USA.
Crit Rev Biochem Mol Biol. 2016 May-Jun;51(3):185-94. doi: 10.3109/10409238.2016.1150958. Epub 2016 Feb 25.
Over the past decade, since epigenetic mechanisms were first implicated in memory formation and synaptic plasticity, dynamic DNA methylation reactions have been identified as integral to long-term memory formation, maintenance, and recall. This review incorporates various new findings that DNA methylation mechanisms are important regulators of non-Hebbian plasticity mechanisms, suggesting that these epigenetic mechanisms are a fundamental link between synaptic plasticity and metaplasticity. Because the field of neuroepigenetics is so young and the biochemical tools necessary to probe gene-specific questions are just now being developed and used, this review also speculates about the direction and potential of therapeutics that target epigenetic mechanisms in the central nervous system and the unique pharmacokinetic and pharmacodynamic properties that epigenetic therapies may possess. Mapping the dynamics of the epigenome in response to experiential learning, even a single epigenetic mark in isolation, remains a significant technical and bioinformatic hurdle facing the field, but will be necessary to identify changes to the methylome that govern memory-associated gene expression and effectively drug the epigenome.
在过去十年中，自从表观遗传机制首次被认为与记忆形成和突触可塑性有关以来，动态DNA甲基化反应已被确定为长期记忆形成、维持和回忆所不可或缺的部分。本综述纳入了各种新发现，即DNA甲基化机制是非赫布可塑性机制的重要调节因子，这表明这些表观遗传机制是突触可塑性和元可塑性之间的基本联系。由于神经表观遗传学领域尚处于起步阶段，用于探究基因特异性问题的生化工具才刚刚开始开发和应用，因此本综述还推测了针对中枢神经系统表观遗传机制的治疗方法的方向和潜力，以及表观遗传疗法可能具有的独特药代动力学和药效学特性。描绘表观基因组对经验性学习的动态反应，即使是单独一个表观遗传标记，仍然是该领域面临的一个重大技术和生物信息学障碍，但这对于识别控制记忆相关基因表达的甲基化组变化以及有效地对表观基因组进行药物干预来说是必要的。
