Integrated profiling identifies long-term molecular consequences of prenatal dexamethasone treatment in the rat brain associated with depression phenotype and cognitive impairment

The study investigates the long-term consequences of prenatal glucocorticoid overexposure in adult rat brains. Our data indicates that dexamethasone, a synthetic glucocorticoid, induces specific changes in DNA methylation in the frontal cortex and hippocampus, in a long-term manner. Analysis revealed that it alters intracellular signal transduction pathways (i.e. cAMP, Ca2+, Wnt, and Hippo signaling pathways), ligand-receptors interactions as well as tight blood-brain barrier formation, which may have an impact on a depressive phenotype observed in prenatally dex-treated rats. The study provides new insights into the molecular mechanisms underlying depressive behaviors and cognition impairment and demonstrates that the dexamethasone administration, besides its beneficial effects, has also the potential to inconveniently modulate numerous signaling pathways in the developing fetal brain, which may have consequences in adulthood.