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

Abstract

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 6 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 5 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 indicative of resiliency in this region. This study provides evidence of the impact of both gestational insult and EE on the regulation of stress responsive genes in the developing brain.

Note:
Funding Information: This project was funded by NIMH under Award Number R15MH114035 (to ACK) and a MCPHS Center for Undergraduate Research Mini-Grant (to MP).

Declaration of Interests: None to declare.

Ethics Approval Statement: Animal procedures were approved by the MCPHS University Institutional Animal Care and Use Committee and carried out in accordance with the recommendations outlined by the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.

Keywords: Early life stress, HPA axis, Developing brain: Psychotic Disorders