Environmental enrichment modulates glucocorticoid receptor expression and reduces anxiety in Indian field male mouse Mus booduga through up-regulation of microRNA-124a

• Standard condition (short-term/long-term) induces anxiety-like behavior in field mouse.
• Enriched condition (EC) decreases anxiety-like behavior.
• Expression of DICER and AGO-2 are up regulated in EC mice.
• EC reduces the expression of GR through up regulation of microRNA-124a.
• EC effectively reverse the effect of short term standard condition.

Enriched environmental condition (EC) has been known to reduce anxiety. In this study, we examined whether an EC could enhance anxiolytic behavior in the Indian field mouse Mus booduga by down-regulating the expression of glucocorticoid receptor (GR) through microRNA-124a. Wild individuals were captured at agricultural field, and then housed at standard conditions (SC) for 7 days. After short-term at standard condition (STSC), on 8th day they were divided into three groups as those: (i) STSC mice tested on light/dark box on the same day and then euthanized to examine gene expression, (ii) maintained at long-term in standard condition (LTSC) and (iii) transferred to EC. After 30 days, both the LTSC and EC groups were tested on the light/dark box and then euthanized to examine gene expression in amygdala region of brain. EC group preferred to stay at light chamber and exhibited less anxiety-like behavioral components when compared to STSC and LTSC groups. However, between the two groups the STSC mice showed lesser anxiety-like behavior than LTSC mice. The expression of Dicer, Ago-2 and microRNA-124a (miR-124a) was more significantly up regulated in EC mice than in STSC and LTSC mice. Furthermore, we have demonstrated that miR-124a binds with 3′UTR of GR, and subsequently we detected a more decreased level of GR in EC than in STSC, LTSC mice. The results suggest that one of the action of EC could be a GR fine tuning through miR-124a, but there is no demonstration that it could be the only involved molecular mechanism.