Early life stress induces age-dependent epigenetic changes in p11 gene expression

Abstract

Early life stress (ELS) causes long-lasting changes in depression-like behaviors 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, behavior phenotypes, 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 depression-like behavior in the forced swimming test. Concurrent with reduced hippocampal p11 levels, mice in both age groups showed decreases in histone acetylation and activating histone methylation as well as increases in repressive histone methylation at the p11 promoter. The extent of the reduction in gene expression and histone acetylation was much higher in middle than in young adulthood. Moreover, 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 depression-like behavior and on the epigenetic modifications of p11 transcription.