Early-life stress induces genome-wide sex-dependent miRNA expression and correlation across limbic brain areas in rats

The aim of this study was to assess regional- and sex-dependent changes in miRNA expression resulting from early-life stress (ELS). Small RNA sequencing was used to determine sex-dependent changes in miRNAs after maternal separation, a rodent model of ELS, across the prefrontal cortex, amygdala and hippocampus. Maternal separation induced anhedonia and altered miRNA expression in a sex-dependent manner, particularly in the prefrontal cortex and hippocampus. Gene ontology revealed that these miRNAs target genes with brain-specific biological functions. Using a network approach to explore miRNA signaling across the brain after ELS, regional differences were highlighted as key to studying the brain’s stress response, which indicates that sex is critical for understanding miRNA-mediated ELS-induced behavior.