Maternal Immune Activation and Enriched Environments Impact B2 SINE Expression in Stress Sensitive Brain Regions of Rodent Offspring.

Early life stress (ELS) can have wide-spread neurodevelopmental effects with support accumulating for the idea that genomic mechanisms may induce lasting physiological and behavioral changes following stress exposure. Previous work found that a sub-family of transposable elements, SINEs, are repressed epigenetically after acute stress. This gives support to the concept that the mammalian genome may be regulating retrotransposon RNA expression allowing for adaptation in response to environmental challenges, such as maternal immune activation (MIA). Transposon (TE) RNAs are now thought to work at the epigenetic level and to have an adaptive response to environmental stressors. Abnormal expression of TEs has been linked to neuropsychiatric disorders like schizophrenia, which is also linked to maternal immune activation. Environmental enrichment (EE), a clinically utilized intervention, is understood to protect the brain, enhance cognitive performance, and attenuate responses to stress. This study examines the effects of MIA on offspring B2 SINE expression and further, the impact that EE, experienced throughout gestation and early life, may have in conjunction with MIA during development. Utilizing RT-PCR to quantify the expression of B2 SINE RNA in the juvenile brain of MIA exposed rat offspring, we found dysregulation of B2 SINE expression associated with MIA in the prefrontal cortex. For offspring experiencing EE, the prefrontal cortex exhibited an attenuation of the MIA response observed in standard housed animals. Here, the adaptive nature of B2 is observed and thought to be aiding in the animal's adaptation to stress. The present changes indicate a wide-spread stress-response system adaptation that impacts not only changes at the genomic level but potentially observable behavioral impacts throughout the lifespan, with possible translational relevance to psychotic disorders.

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.