Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory
Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory
复制标题
海马 dCA1 条件性 Dnmt3b 缺失损害识别记忆
DOI：
10.1186/s13041-020-00574-9
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发表时间：
2020-03-17
期刊：
影响因子：
3.6
通讯作者：
Zhou, Yu
中科院分区：
文献类型：
--
作者：
Kong, Qingnuan;Yu, Ming;Zhou, Yu
目的神经元DNA甲基化和去甲基化的主动变化似乎是学习记忆形成过程中突触缩放和谷氨酸受体运输的控制者。DNA甲基转移酶（DNMTs）包括Dnmt 1、Dnmt 3a和Dnmt 3b编码的蛋白质，是进行DNA甲基化的主要酶。我们前期的研究证实了DNMT 1和DNMT 3a在突触功能和记忆中的重要作用。本研究旨在探讨DNMT 3b及其介导的DNA甲基化在记忆过程中的作用。方法采用腺相关病毒（AAV-syn-Cre-GFP）基因转染技术，在成年小鼠海马CA 1区特异性敲除Dnmt 3b。行为测试用于评估记忆性能。通过基因表达谱芯片分析和定量RT-PCR技术寻找差异表达基因。结果与对照组相比，感染Cre病毒的Dnmt 3b（flox/flox）小鼠新物体位置识别（NPR）受损，新物体识别（NOR）正常。微阵列分析揭示了接受Cre病毒注射的Dnmt 3b（flox/flox）小鼠海马中K+通道亚基的差异表达。通过以下qRT-PCR分析证实Kcne 2表达增加。我们还发现NPR训练和测试诱导对照小鼠海马Dnmt 1和Dnmt 3a mRNA表达上调，但在Cre病毒注射小鼠中没有。因此，我们的研究结果表明，海马子区域中的条件性Dnmt 3b缺失损害了一种特定形式的识别记忆，这种识别记忆是海马依赖的。
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 Dnmt3b(flox/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 Dnmt3b(flox/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.