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

Abstract

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.

Sex-Specific Differences and the Role of Environmental Enrichment in the Expression of Hippocampal CB1 Receptors following Chronic Unpredictable Stress

“…Specifically, the learning impairments previously found exclusively in CUS males could be associated with the decreases found in SYN and CB 1 receptor expression in the CA3 and CA1 hippocampal areas. Meanwhile, the decreases in SYN and CB 1 receptor expression in CA1 observed in females may explain the increase in depressive behavior detected only in females [38,39]. In support of the present findings, existing evidence highlights the role of eCBs in modulating synaptic function and contributing to synaptic plasticity through retrograde signaling to CB 1 and CB 2 receptors [58].…”

“…Based on our findings, the adverse effects of CUS on cognitive function and emotional behavior [38], which were also linked to a region and sex-specific decrease in the expression of glial fibrillary acidic protein (GFAP) and synaptophysin (SYN) in the hippocampus [39], may be mediated by alterations in the CB 1 receptor expression. Specifically, the learning impairments previously found exclusively in CUS males could be associated with the decreases found in SYN and CB 1 receptor expression in the CA3 and CA1 hippocampal areas.…”

“…The DAB signal was blindly quantified and analyzed using the ImageJ/Fiji software (version 1.2). The mean percentage of CB 1 -positive tissue area per hippocampal region was calculated as an indicator of CB 1 immunoreactivity (for more details, see [39]).…”

“…The enriched environment (EE), described as "a new way of endogenous pharmacotherapy" [37], acts protectively against the negative effects induced by stressful experiences [38][39][40] and exerts significant molecular, anatomical and functional changes in the brain [41]. In animal studies, the EE condition refers to the housing of more than two same-sex animals in large cages equipped with various objects of varying shapes and sizes along with running wheels.…”