Environmental enrichment enhances sociability by regulating glutamate signaling pathway through GR by epigenetic mechanisms in amygdala of Indian field mice Mus booduga

Abstract

Environmental enrichment (EE) dynamically regulates gene expression and synaptic plasticity with positive consequences on behavior. The present study was performed on field-mice to explore the effects of EE on both captive-condition inducing social stress and epigenetic changes of molecules resilience stress. For this purpose, field-mice were caught and allowed to habituate in standard laboratory conditions for 7 days. The next day animals were randomly assigned to three groups: i) mice at short-term standard condition (STSC); which were subjected to social interaction test (SIT) on day 9, ii) mice continuously maintainedfor additional 30 days, with these long-term standard conditions (LTSC), and iii) mice maintained in an EE cage for additional 30 days. After achieving SIT, we examined epigenetic changes of a repertory of molecules associated with resilience stress, by determining their levels by Western blot. Thus, the main findings were that during SIT, EE exerted more social interaction of field-mice with the strangers compared with STSC and LTSC mice. Related with social behavior results, we found that in mice subjected to EE the levels of histone 3 lysine 9 di-methylation (H3K9me2), glucocorticoid receptor (GR), N-methyl-D asparate (NMDA) receptor subunits NR2A and NR2B, postsynaptic density protein-95 (PSD-95), and mature brain-derived neurotrophic factor (mBDNF) were significantly elevated; whereas the levels of DNA methyltransferase-3A (DNMT3A), methyl-CpG-binding protein-2 (MeCP2), repressor element-1 silencing transcription factor (REST), H3K4me2 and lysine demethylase-1A (KDM1A) decreased. These results suggest that enhanced sociability of EE mice could be mediated, in part, by altered expression of molecules regulating glutamate signaling pathway through GR by epigenetic mechanisms.