Epigenetic modification of glucocorticoid receptor promoter I7 in maternally separated and restraint-stressed rats

Abstract

Glucocorticoid receptor (GR) promoter I7 is susceptible to epigenetic changes induced by environmental influences. Early life stress (ELS) has a persistent impact on GR expression, as well as behavior, in adult rodents via epigenetic changes of GR promoter I7. Moreover, various stressors can induce histone modifications in this region during adulthood. Thus, the present study aimed to investigate whether maternally separated (MS) rats exposed to chronic restraint stress (RS) would exhibit histone modifications of GR promoter I7 in the hippocampus. Rats were subjected to MS (3h per day) on postnatal days (PND) 1–21. Then, during adulthood (PND 56–77), the rats were exposed to RS (2h per day) followed by treatment with escitalopram (10mg/kg). The MS and RS groups exhibited significant decreases in total and exon I7 GR mRNA levels and the combination of MS and RS exerted a greater effect on these mRNA levels than either MS or RS alone. Additionally, both the MS and RS groups showed significant reductions in histone H3 acetylation at GR promoter I7 and the combination of MS and RS had a greater effect than did either MS or RS alone. Chronic escitalopram treatment ameliorated these changes. The present results indicate that postnatal MS and adult RS influence GR expression through histone modification at GR promoter I7, and that the combination of the two stressors potentiates these changes. Furthermore, epigenetic mechanisms are involved in escitalopram action.