Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory

Abstract 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...

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Main Authors: Qingnuan Kong, Ming Yu, Meng Zhang, Chuang Wei, Huating Gu, Shaoyang Yu, Wei Sun, Nan Li, Yu Zhou
Format: Article
Language:English
Published: BMC 2020-03-01
Series:Molecular Brain
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13041-020-00574-9
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author Qingnuan Kong
Ming Yu
Meng Zhang
Chuang Wei
Huating Gu
Shaoyang Yu
Wei Sun
Nan Li
Yu Zhou
author_facet Qingnuan Kong
Ming Yu
Meng Zhang
Chuang Wei
Huating Gu
Shaoyang Yu
Wei Sun
Nan Li
Yu Zhou
author_sort Qingnuan Kong
collection DOAJ
description Abstract 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.
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spelling doaj.art-bc3cea64c4384d0fb077863881944c4a2022-12-21T19:05:17ZengBMCMolecular Brain1756-66062020-03-011311410.1186/s13041-020-00574-9Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memoryQingnuan Kong0Ming Yu1Meng Zhang2Chuang Wei3Huating Gu4Shaoyang Yu5Wei Sun6Nan Li7Yu Zhou8Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Qingdao UniversityAbstract 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.http://link.springer.com/article/10.1186/s13041-020-00574-9Dnmt3bMemoryHippocampusObject-place recognition
spellingShingle Qingnuan Kong
Ming Yu
Meng Zhang
Chuang Wei
Huating Gu
Shaoyang Yu
Wei Sun
Nan Li
Yu Zhou
Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory
Molecular Brain
Dnmt3b
Memory
Hippocampus
Object-place recognition
title Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory
title_full Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory
title_fullStr Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory
title_full_unstemmed Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory
title_short Conditional Dnmt3b deletion in hippocampal dCA1 impairs recognition memory
title_sort conditional dnmt3b deletion in hippocampal dca1 impairs recognition memory
topic Dnmt3b
Memory
Hippocampus
Object-place recognition
url http://link.springer.com/article/10.1186/s13041-020-00574-9
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