The role of active DNA demethylation and Tet enzyme function in memory formation and cocaine action.
The role of active DNA demethylation and Tet enzyme function in memory formation and cocaine action.
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DOI：
10.1016/j.neulet.2016.01.023
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发表时间：
2016-06-20
影响因子：
2.5
通讯作者：
Wood MA
中科院分区：
文献类型：
--
作者：
Alaghband Y;Bredy TW;Wood MA
主动DNA修饰是以经验依赖性方式调节基因表达的主要表观遗传机制，其被认为建立神经元功能和行为的稳定变化。最近关于DNA羟化酶10 - 11易位（Tet 1 -3）家族的发现为活性DNA去甲基化的研究提供了新的途径，因此可能有助于促进我们了解动态DNA修饰如何导致学习和记忆相关脑区的持久变化，以及戒毒后的药物寻求和复发倾向。药物成瘾是一种复杂的复发性疾病，其中强迫性药物寻求行为可以持续存在，尽管后果令人厌恶。因此，了解药物成瘾的发生和持续的分子机制，以及在成瘾者中观察到的明显的复发倾向，对于发展选择性治疗和疗法是必要的。在这篇小型评论中，我们概述了主动DNA去甲基化的参与，重点是泰特酶家族和5-羟甲基胞嘧啶（5-hmC）在学习和记忆以及药物寻求行为中的作用。记忆和成瘾共享重叠的分子，细胞和电路功能，允许一个领域的研究为另一个领域提供信息。目前的差异和未来的研究方向集中在DNA甲基化和去甲基化之间的动态相互作用，以及它们如何编排所需的神经元可塑性的记忆形成的基因表达，进行了讨论。
Active DNA modification is a major epigenetic mechanism that regulates gene expression in an experience-dependent manner, which is thought to establish stable changes in neuronal function and behavior. Recent discoveries regarding the Ten eleven translocation (Tet1-3) family of DNA hydroxylases have provided a new avenue for the study of active DNA demethylation, and may thus help to advance our understanding of how dynamic DNA modifications lead to long-lasting changes in brain regions underlying learning and memory, as well as drug-seeking and propensity for relapse following abstinence. Drug addiction is a complex, relapsing disorder in which compulsive drug-seeking behavior can persist despite aversive consequences. Therefore, understanding the molecular mechanisms that underlie the onset and persistence of drug addiction, as well as the pronounced propensity for relapse observed in addicts, is necessary for the development of selective treatments and therapies. In this mini-review, we provide an overview of the involvement of active DNA demethylation with an emphasis on the Tet family of enzymes and 5-hydroxymethylcytosine (5-hmC) in learning and memory, as well as in drug-seeking behavior. Memory and addiction share overlapping molecular, cellular, and circuit functions allowing research in one area to inform the other. Current discrepancies and directions for future studies focusing on the dynamic interplay between DNA methylation and demethylation, and how they orchestrate gene expression required for neuronal plasticity underlying memory formation, are discussed.