Environmental enrichment initiated in adolescence restores the reduced expression of synaptophysin and GFAP in the hippocampus of chronically stressed rats in a sex-specific manner

This study aims at investigating whether environmental enrichment (EE) initiated in adolescence can alter chronic unpredictable stress (CUS)-associated changes in astroglial and synaptic plasticity markers in male and female rats. To this end, we studied possible alterations in hippocampal glial fibrillary acidic protein (GFAP) and synaptophysin (SYN) in CUS rats previously housed in EE. Wistar rats on postnatal day (PND) 23 were housed for 10 weeks in standard housing (SH) or enriched conditions. On PND 66, animals were exposed to CUS for 4 weeks. SYN and GFAP expressions were evaluated in CA1 and CA3 subfields and dentate gyrus (DG). CUS reduced the expression of SYN in all hippocampal areas, whereas lower GFAP expression was evident only in CA1 and CA3. The reduced expression of SYN in DG and CA3 was evident to male SH/CUS rats, whereas the reduced GFAP expression in CA1 and CA3 was limited to SH/CUS females. EE housing increased the hippocampal expression of both markers and protected against CUS-associated decreases. Our findings indicate that the decreases in the expression of SYN and GFAP following CUS are region and sex-specific and underline the neuroprotective role of EE against these CUS-associated changes.