Dnmt3a2: a hub for enhancing cognitive functions
Dnmt3a2: a hub for enhancing cognitive functions
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DOI：
10.1038/mp.2015.175
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发表时间：
2016-08-01
影响因子：
11
通讯作者：
Bading, H.
中科院分区：
文献类型：
--
作者：
Oliveira, A. M. M.;Hemstedt, T. J.;Bading, H.
恐惧记忆形成和消失的机制还远未被理解。揭示调节这些过程的分子和机制对于确定开发焦虑和恐惧障碍新型治疗策略的分子靶点至关重要。认知能力需要激活基因表达，这是巩固神经元功能持久变化所必需的。在这项研究中，我们建立了一个关键作用的表观遗传因素，从头DNA甲基转移酶，Dnmt 3a 2，在记忆的形成和灭绝。我们发现，Dnmt 3a 2在年轻成年小鼠海马中的过表达在各种情况下诱导记忆增强;它将弱学习经历转化为长期记忆，增强恐惧记忆形成并促进恐惧记忆消退。Dnmt 3a 2的过表达也与可塑性相关基因的表达增加有关。此外，Dnmt 3a 2表达的敲低损害了动物消除记忆的能力，将Dnmt 3a 2确定为灭绝的关键参与者。因此，Dnmt 3a 2是记忆过程的核心，代表了认知增强疗法的新靶点，以改善焦虑和恐惧障碍并促进记忆巩固。
The mechanisms responsible for fear memory formation and extinction are far from being understood. Uncovering the molecules and mechanisms regulating these processes is vital for identifying molecular targets for the development of novel therapeutic strategies for anxiety and fear disorders. Cognitive abilities require the activation of gene expression necessary to the consolidation of lasting changes in neuronal function. In this study we established a key role for an epigenetic factor, the de novo DNA methyltransferase, Dnmt3a2, in memory formation and extinction. We found that Dnmt3a2 overexpression in the hippocampus of young adult mice induced memory enhancements in a variety of situations; it converted a weak learning experience into long-term memory, enhanced fear memory formation and facilitated fear memory extinction. Dnmt3a2 overexpression was also associated with the increased expression of plasticity-related genes. Furthermore, the knockdown of Dnmt3a2 expression impaired the animals' ability to extinguish memories, identifying Dnmt3a2 as a key player in extinction. Thus, Dnmt3a2 is at the core of memory processes and represents a novel target for cognition-enhancing therapies to ameliorate anxiety and fear disorders and boost memory consolidation.