Prenatal Administration of Dexamethasone Leads to Decreased Lysine 24 Acetylation of Histone H3 in the Neocortex and Hippocampus of Adult Rats

Dexamethasone, as well as other synthetic glucocorticoids, is widely employed in general obstetric practice. The principal indication for glucocorticoid treatment is a risk of miscarriage. However, certain data suggest that glucocorticoid administration during pregnancy may lead to aberrations of brain development and behavior in the offspring. Current research suggests that such aberrations are frequently mediated by epigenetic mechanisms. The goal of the present work was to investigate the patterns of histone H3 acetylation at lysine 24 (acH3K24) in neurons of the hippocampus and the neocortex of adult rats following administration of dexamethasone (0.8 mg/kg) in the beginning and the end of week 3 of their prenatal development. Immunohistochemical analysis was used to describe changes in the acH3K24 content in the cells of the hippocampus and the neocortex of adult rats after exposure to dexamethasone on gestation days 14–16 and 17–19. The principal differences concerned the number of cells strongly stained with acH3K24-specific antibodies. In particular, exposure to dexamethasone led to a decrease in the number of cells with a high acH3K24 content in the CA1 field and the dentate gyrus of the hippocampal formation, Specifically, this decrease constituted 53.5 and 76% in CA1 and 39.7 and 87.8% in the dentate gyrus following dexamethasone administration on gestation days 14–16 and 17–19, respectively. In cortical layer 5, the abundance of acH3K24 decreased (to 55% of the control level) following dexamethasone administration on gestation days 17–19, but not on days 14–16. The observed modifications of the epigenetic status of brain cells of rats exposed to dexamethasone may underlie the long-lasting changes in behavior and learning capacity described in our previous studies.