Maternal upbringing and selective breeding for voluntary exercise behavior modify patterns of DNA methylation and expression of genes in the mouse brain
Sarah E. Latchney, Marcell D. Cadney, Anthony Hopkins, Theodore Garland Jr
{"title":"Maternal upbringing and selective breeding for voluntary exercise behavior modify patterns of DNA methylation and expression of genes in the mouse brain","authors":"Sarah E. Latchney, Marcell D. Cadney, Anthony Hopkins, Theodore Garland Jr","doi":"10.1111/gbb.12858","DOIUrl":null,"url":null,"abstract":"<p>Selective breeding has been utilized to study the genetic basis of exercise behavior, but research suggests that epigenetic mechanisms, such as DNA methylation, also contribute to this behavior. In a previous study, we demonstrated that the brains of mice from a genetically selected high runner (HR) line have sex-specific changes in DNA methylation patterns in genes known to be genomically imprinted compared to those from a non-selected control (C) line. Through cross-fostering, we also found that maternal upbringing can modify the DNA methylation patterns of additional genes. Here, we identify an additional set of genes in which DNA methylation patterns and gene expression may be altered by selection for increased wheel-running activity and maternal upbringing. We performed bisulfite sequencing and gene expression assays of 14 genes in the brain and found alterations in DNA methylation and gene expression for <i>Bdnf</i>, <i>Pde4d</i> and <i>Grin2b</i>. Decreases in <i>Bdnf</i> methylation correlated with significant increases in <i>Bdnf</i> gene expression in the hippocampus of HR compared to C mice. Cross-fostering also influenced the DNA methylation patterns for <i>Pde4d</i> in the cortex and <i>Grin2b</i> in the hippocampus, with associated changes in gene expression. We also found that the DNA methylation patterns for <i>Atrx</i> and <i>Oxtr</i> in the cortex and <i>Atrx</i> and <i>Bdnf</i> in the hippocampus were further modified by sex. Together with our previous study, these results suggest that DNA methylation and the resulting change in gene expression may interact with early-life influences to shape adult exercise behavior.</p>","PeriodicalId":50426,"journal":{"name":"Genes Brain and Behavior","volume":"22 6","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2023-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/gbb.12858","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes Brain and Behavior","FirstCategoryId":"102","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/gbb.12858","RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Selective breeding has been utilized to study the genetic basis of exercise behavior, but research suggests that epigenetic mechanisms, such as DNA methylation, also contribute to this behavior. In a previous study, we demonstrated that the brains of mice from a genetically selected high runner (HR) line have sex-specific changes in DNA methylation patterns in genes known to be genomically imprinted compared to those from a non-selected control (C) line. Through cross-fostering, we also found that maternal upbringing can modify the DNA methylation patterns of additional genes. Here, we identify an additional set of genes in which DNA methylation patterns and gene expression may be altered by selection for increased wheel-running activity and maternal upbringing. We performed bisulfite sequencing and gene expression assays of 14 genes in the brain and found alterations in DNA methylation and gene expression for Bdnf, Pde4d and Grin2b. Decreases in Bdnf methylation correlated with significant increases in Bdnf gene expression in the hippocampus of HR compared to C mice. Cross-fostering also influenced the DNA methylation patterns for Pde4d in the cortex and Grin2b in the hippocampus, with associated changes in gene expression. We also found that the DNA methylation patterns for Atrx and Oxtr in the cortex and Atrx and Bdnf in the hippocampus were further modified by sex. Together with our previous study, these results suggest that DNA methylation and the resulting change in gene expression may interact with early-life influences to shape adult exercise behavior.
期刊介绍:
Genes, Brain and Behavior was launched in 2002 with the aim of publishing top quality research in behavioral and neural genetics in their broadest sense. The emphasis is on the analysis of the behavioral and neural phenotypes under consideration, the unifying theme being the genetic approach as a tool to increase our understanding of these phenotypes.
Genes Brain and Behavior is pleased to offer the following features:
8 issues per year
online submissions with first editorial decisions within 3-4 weeks and fast publication at Wiley-Blackwells
High visibility through its coverage by PubMed/Medline, Current Contents and other major abstracting and indexing services
Inclusion in the Wiley-Blackwell consortial license, extending readership to thousands of international libraries and institutions
A large and varied editorial board comprising of international specialists.