Abstract
AimActive 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.MethodsDnmt3b 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.ResultsDnmt3bflox/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.
Highlights
It is well-known that DNA methylation alters gene expression without changing DNA sequence, and it plays a vital role in regulating adult brain functions including learning and memory [1, 2]
We found that novel object-place recognition (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 demonstrate that conditional Dnmt3b deletion in a subregion of the hippocampus impairs a specific form of recognition memory that is hippocampus-dependent
Summary
It is well-known that DNA methylation alters gene expression without changing DNA sequence, and it plays a vital role in regulating adult brain functions including learning and memory [1, 2]. Kong et al Molecular Brain (2020) 13:42 are closely associated with learning and memory processes [4, 5]. Our previous findings showed that double knockout of Dnmt and Dnmt3a in αCaMKII+ forebrain neurons led to hippocampus-dependent memory impairment [1]. In spite of very limited expression in mature neurons, several studies have suggested that DNMT3b, when concurrently functioning with DNMT1 or DNMT3a to modulate DNA methylation, may play an important role in controlling gene expression and memory processes [6–8]. DNMT3b alone has been proven to play specific roles in regulating methylation and certain brain functions.
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