Abstract
Early life stress (ELS) causes long-lasting changes in gene expression through epigenetic mechanisms. However, little is known about the effects of ELS in adulthood, specifically across different age groups. In this study, the epigenetic modifications of p11 expression in adult mice subjected to ELS were investigated in different stages of adulthood. Pups experienced maternal separation (MS) for 3 h daily from postnatal day 1 to 21. At young and middle adulthood, behavioral test, hippocampal p11 expression levels, and levels of histone acetylation and methylation and DNA methylation at the hippocampal p11 promoter were measured. Middle-aged, but not young adult, MS mice exhibited increased immobility time in the forced swimming test. Concurrent with reduced hippocampal p11 levels, mice in both age groups showed a decrease in histone acetylation (AcH3) and permissive histone methylation (H3K4me3) at the p11 promoter, as well as an increase in repressive histone methylation (H3K27me3). Moreover, our results showed that the expression, AcH3 and H3Kme3 levels of p11 gene in response to MS were reduced with age. DNA methylation analysis of the p11 promoter revealed increased CpG methylation in middle-aged MS mice only. The results highlight the age-dependent deleterious effects of ELS on the epigenetic modifications of p11 transcription.
Highlights
Life stress (ELS) causes long-lasting changes in gene expression through epigenetic mechanisms
These studies are focused on the epigenetic mechanisms, for example, DNA methylation and histone modification, by which Early life stress (ELS) may alter the expression of genes involved in the stress response, including brain-derived neurotrophic factor (BDNF), glucocorticoid receptor (GR; NR3C1), and corticotrophin-releasing factor[3,4]
This paper reports that maternal separation (MS) in early life exerts negative effects on epigenetic mechanisms associated with decreased p11 expression in adulthood, and these effects become more pronounced with age
Summary
Life stress (ELS) causes long-lasting changes in gene expression through epigenetic mechanisms. In human and animal studies, ELS has been reported to induce a depression-like phenotype in adulthood[3,4] These studies are focused on the epigenetic mechanisms, for example, DNA methylation and histone modification, by which ELS may alter the expression of genes involved in the stress response, including brain-derived neurotrophic factor (BDNF), glucocorticoid receptor (GR; NR3C1), and corticotrophin-releasing factor[3,4]. The emphasis of these papers is mainly on the detrimental effects of ELS. Exposure to caregiver maltreatment alters the level of expression of genes important in regulating DNA methylation patterns (Dnmt[1], Dnmt3a, MeCP2, Gadd45b and Hdac1) in the adult medial prefrontal cortex[12]
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