Abstract
Positive experiences in early life may improve the capacity to cope with adulthood stress through epigenetic modification. We investigated whether an enriched environment (EE) in the postnatal period affected epigenetic changes in the p11 gene induced by chronic unpredictable stress (CUS) in adult C57BL/6J mice. EE was introduced for 5 weeks during postnatal days 21–55. After EE, the mice were subjected to CUS for 4 weeks. EE prevented depression-like behavior induced by adult CUS. EE prevented a decrease in p11 mRNA and histone H3 acetylation induced by CUS, with changes in the expression of histone deacetylase 5. Moreover, EE prevented changes in trimethylation of histone H3 lysine 4 (H3K4) and H3K27 induced by CUS. Furthermore, EE had positive effects on behavior and epigenetic alterations in adult mice without CUS. These results suggest that one of the underlying mechanisms of early-life EE may involve epigenetic modification of the hippocampal p11 gene promoter.
Highlights
We investigated whether early EE after weaning can induce long-lasting effects on depression-like behavior induced by adulthood stress and whether the effects of EE are involved in epigenetic modification of the p11 gene
EE is already well known for its positive effects on depressionlike and anxiety-like behaviors in human and animal models
Our behavioral data demonstrate that early EE prevented the behavioral despair state induced by chronic unpredictable stress (CUS) during adulthood, suggesting that early EE improves the ability to cope with stress under an unpredictable stress situation, as in CUS
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Numerous studies have indicated that adverse experiences in early life augment the risk of depression in adulthood and that this effect is influenced by epigenetic mechanisms [3,4,5]. Expression of p11, called S100A10, plays a critical role in depression-like behaviors and responses to antidepressant drugs [14]. P11 expression is regulated by brain-derived neurotropic factor (BDNF), which plays important roles in neural plasticity and neurogenesis in the hippocampus, and the antidepressant-like effects of BDNF depend on p11 [17]. We investigated whether early EE after weaning can induce long-lasting effects on depression-like behavior induced by adulthood stress and whether the effects of EE are involved in epigenetic modification of the p11 gene. We employed chronic unpredictable stress (CUS), an animal model of depression, as a form of adult stress
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