Genomic and Epigenomic Responses to Chronic Stress Involve miRNA-Mediated Programming

Stress represents a critical influence on motor system function and has been shown to impair movement performance. We hypothesized that stress-induced motor impairments are due to brain-specific changes in miRNA and protein-encoding gene expression. Here we show a causal link between stress-induced motor impairment and associated genetic and epigenetic responses in relevant central motor areas in a rat model. Exposure to two weeks of mild restraint stress altered the expression of 39 genes and nine miRNAs in the cerebellum. In line with persistent behavioural impairments, some changes in gene and miRNA expression were resistant to recovery from stress. Interestingly, stress up-regulated the expression of Adipoq and prolactin receptor mRNAs in the cerebellum. Stress also altered the expression of Prlr, miR-186, and miR-709 in hippocampus and prefrontal cortex. In addition, our findings demonstrate that miR-186 targets the gene Eps15. Furthermore, we found an age-dependent increase in EphrinB3 and GabaA4 receptors. These data show that even mild stress results in substantial genomic and epigenomic changes involving miRNA expression and associated gene targets in the motor system. These findings suggest a central role of miRNA-regulated gene expression in the stress response and in associated neurological function

Adrenergic hormones induce extrapituitary prolactin gene expression in leukocytes-potential implications in obesity

Abstract The pituitary hormone prolactin (PRL), originally described for its role in lactation, has been implemented in over 300 functions and is produced by multiple cell types outside of the pituitary. Monocyte/macrophages in particular show robust expression of extra-pituitary prolactin (ePRL). While ePRL protein is identical to pituitary PRL and translated from the same gene, tissues outside the pituitary engage an alternative promoter to regulate expression. Many of the factors regulating this expression, however, remain unknown. Here we show that the adrenergic hormones epinephrine and norepinephrine induce PRL expression in the human monocytic cell line THP-1 at physiological concentrations. Furthermore, our experiments show the polarization state of differentiated macrophages can influence their response in vitro, with inflammatory M1 macrophages—common in obese adipose—showing the highest levels of PRL expression compared to other macrophage types. Adrenergic hormones have a clearly defined role in adipocyte lipid metabolism, stimulating lipolysis through hormone sensitive lipase (HSL) induction. Meanwhile, PRL has been shown to stimulate lipogenesis. This highlights ePRL production as a possible factor in obesity. The overall balance of these two signals could play a critical role in determining overall lipid turnover/accumulation in adipose depots where large numbers of adipose tissue macrophages (ATMs) reside