AIM Active changes in neuronal DNA methylation and demethylation appear to act as controllers of synaptic scaling and glutamate receptor trafficking in learning and memory formation. DNA methyltransferases (DNMTs), including proteins encoded by Dnmt1, Dnmt3a and Dnmt3b, are dominant enzymes carrying out DNA methylation. Our previous study demonstrated the important roles that DNMT1 and DNMT3a play in synaptic function and memory. In this study, we aim to explore the role of DNMT3b and its-mediated DNA methylation in memory processes. METHODS Dnmt3b was knocked down specifically in dorsal CA1 neurons of adult mice hippocampus by AAV-syn-Cre-GFP virus injection. Behavioral tests were used to evaluate memory performance. Gene expression microarray analysis followed by quantitative RT-PCR were performed to find differential expression genes. RESULTS Dnmt3bflox/flox mice receiving Cre-virus infection showed impaired novel object-place recognition (NPR) and normal novel object recognition (NOR), in comparison to mice receiving control GFP-virus infection. Microarray analysis revealed differential expression of K+ channel subunits in the hippocampus of Dnmt3bflox/flox mice receiving Cre-virus injection. Increased Kcne2 expression was confirmed by following qRT-PCR analysis. We also found that NPR training and testing induced up-regulation of hippocampal Dnmt1 and Dnmt3a mRNA expression in control mice, but not in Cre-virus injected mice. Our findings thus demonstrate that conditional Dnmt3b deletion in a sub-region of the hippocampus impairs a specific form of recognition memory that is hippocampus-dependent.

中文翻译：

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海马 dCA1 中的条件性 Dnmt3b 缺失会损害识别记忆。


目的 神经元 DNA 甲基化和去甲基化的活跃变化似乎是学习和记忆形成中突触缩放和谷氨酸受体运输的控制器。 DNA 甲基转移酶 (DNMT)，包括由 Dnmt1、Dnmt3a 和 Dnmt3b 编码的蛋白质，是进行 DNA 甲基化的主要酶。我们之前的研究证明了 DNMT1 和 DNMT3a 在突触功能和记忆中发挥的重要作用。在本研究中，我们旨在探讨 DNMT3b 及其介导的 DNA 甲基化在记忆过程中的作用。方法通过AAV-syn-Cre-GFP病毒注射，特异性敲低成年小鼠海马背侧CA1神经元中的Dnmt3b。行为测试用于评估记忆表现。进行基因表达微阵列分析，然后进行定量 RT-PCR，以发现差异表达基因。结果与接受对照 GFP 病毒感染的小鼠相比，接受 Cre 病毒感染的 Dnmt3bflox/flox 小鼠表现出新物体位置识别（NPR）受损和正常新物体识别（NOR）。微阵列分析揭示了接受 Cre 病毒注射的 Dnmt3bflox/flox 小鼠海马中 K+ 通道亚基的差异表达。通过 qRT-PCR 分析证实 Kcne2 表达增加。我们还发现，NPR 训练和测试诱导对照小鼠海马 Dnmt1 和 Dnmt3a mRNA 表达上调，但在注射 Cre 病毒的小鼠中则不然。因此，我们的研究结果表明，海马体某个亚区域的条件性 Dnmt3b 缺失会损害海马体依赖性的特定形式的识别记忆。