Abstract
Growing evidence suggests that early life stress (ELS) has long-lasting effects on glucocorticoid receptor (GR) expression and behavior via epigenetic changes of the GR exon 17 promoter. However, it remains unclear whether ELS regulates histone modifications of the GR exon 17 promoter across the life span. We investigated the effects of maternal separation (MS) on histone acetylation and methylation of GR exon 17 promoter in the hippocampus, according to the age of adults. Depression-like behavior and epigenetic regulation of GR expression were examined at young and middle adulthood in mice subjected to MS from postnatal day 1 to 21. In the forced swimming test, young adult MS mice showed no effect on immobility time, but middle-aged MS mice significantly increased immobility time. Young adult and middle-aged MS mice showed decreased GR expression. Their two ages showed decreased histone acetylation with increased histone deacetylases (HDAC5) levels, decreased permissive methylation, and increased repressive methylation at the GR exon 17 promoter. The extent of changes in gene expression and histone modification in middle adulthood was greater than in young adulthood. These results indicate that MS in early life causes long-term negative effects on behavior via histone modification of the GR gene across the life span.
Highlights
Life stress (ELS) refers to various types of abuse by parents or caregivers that children and adolescents may experience such as child abuse, neglect, and loss [1]
We investigated the effect of maternal separation (MS) on depression-like behavior using forced swimming test (FST) in young adults and middle-aged MS mice and their age-matched controls (Figure 2)
We investigated how postnatal MS affects glucocorticoid receptor (GR) expression and epigenetic modifications in young and middle adulthood in mice
Summary
Life stress (ELS) refers to various types of abuse by parents or caregivers that children and adolescents may experience such as child abuse, neglect, and loss [1]. Many human and animal studies have verified that ELS causes epigenetic changes in the glucocorticoid receptor (GR) gene (NR3C1), which regulates gene expression and behavior in adults [5,6,7]. Among the first exon promoters, the exon 17 (exon IF homolog in human) promoter is responsive to DNA methylation induced by ELS, which causes a decrease in GR expression in rodents and humans [9]. At this time, most studies on epigenetic changes in the GR exon 17/1F promoter induced by ELS have focused on DNA methylation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
