Glucocorticoid Receptor Stimulation Resulting from Early Life Stress Affects Expression of DNA Methyltransferases in Rat Prefrontal Cortex

AbstractEarly life stress initiates long-term neurobiological changes that affect stress resilience and increased susceptibility to psychopathology. Maternal separation (MS) is used to cause early life stress and it induces profound neurochemical and behavioral changes that last until adulthood. The molecular pathways of how MS affects the regulation of DNA methyltransferases (Dnmt) in brain have not been entirely characterized. We evaluated MS effects onDnmt1, Dnmt3a andDnmt3b expression, DNMT enzyme activity and glucocorticoid receptor (GR) recruitment to differentDnmt loci in the prefrontal cortex (PFC) of Wistar rats. We found increased plasma corticosterone levels after MS that were associated with inducedDnmt expression and enzyme activity in rat PFC at post-natal day 15 (PND15). Chromatin immunoprecipitation showed increased binding of GR at theDnmt3b promoter after MS, suggesting that genomic signaling of GR is an important regulatory mechanism for the inducedDnmt3b expression and DNMT activity. Although GR also binds toDnmt3a promoter and a putative regulatory region in intron 3 in rat PFC, its expression after maternal separation may be influenced by other mechanisms. Therefore, GR could be a link between early life stress experience and long-term gene expression changes induced by aberrant DNA methylation.
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research