Regulatory Effects of Maternal Immune Activation and Environmental Enrichment on Glucocorticoid Receptor and FKBP5 Expression in Stress-sensitive Regions of the Offspring Brain.

A mother's exposure to immune challenge during pregnancy is well known to be a detrimental factor to the development of the offspring's brain and an impetus for neuropsychiatric disorders. Previous studies have shown that these adverse events can dysregulate the stress response machinery. Two crucial components of the stress axis considered to be affected have been targets in these studies: the glucocorticoid receptor (GR), and FKBP5 which regulates GR activity. The implementation of interventions such as Environmental Enrichment (EE) have shown positive results in protecting the brain against the consequences associated with gestational insults. In light of this, we investigated the transcriptional regulation of GR and FKBP5 from six stress-sensitive brain regions of the offspring using a rat model of maternal immune activation (MIA). Furthermore, we analyzed the effect of an enriched environment on their expression. We found an increase in FKBP5 in MIA rats in five brain regions. RT-qPCR analysis of MIA's effect on GR yielded insignificant results. However, we found that EE increased GR expression in the medial preoptic area which could be indicative of a positive regulation by EE. This study provides evidence of the impact of both gestational insult and EE on the regulation of stress responsive genes in the developing brain.