The characteristics of acetylation of histone H3 at Lys24 in the hippocampus and neocortex of rats that were exposed to hypoxic stress at different stages of prenatal development

Abstract

Hypoxic stress has a considerable effect on fetal development and may lead to irreversible longterm developmental disorders of the brain, increasing the risk of neurological complications. Modern research shows that epigenetic mechanisms may play a key role in the development of these pathologies. Here, we studied histone H3 acetylation at lysine 24 in the neurons of the brain structures that are most sensitive to hypoxia (hippocampus and neocortex) after severe hypobaric hypoxia (180 mmHg, 3 h) on the 14–16th and 17–19th days of prenatal ontogeny. Using the immunohistochemical method, it was found that severe hypobaric hypoxia on the 14–16th and 17th–19th days of prenatal ontogeny leads to a prolonged (at least up to 3 months) decrease in the degree of acetylation of histone H3 at lysine 24, but not general histone acetylation, in the hippocampus and neocortex of rats. The intensity of changes depends both on the time of the presentation of hypoxia, and on the areas of the brain that are studied. Thus, in the CA1 region and the dentate gyrus of the hippocampus, hypoxia leads to more-pronounced changes in the number of immunopositive cells and cells with intense immunostaining to the H3 histones acetylated at lysine 24 than in the fifth layer of the neocortex. This may be due to the mismatch between the critical periods of the development of different regions of the brain and the differences in their sensitivity to hypoxia. The discovered modifications of the epigenetic status of brain cells in rats that were subjected to prenatal hypoxia may underlie previously shown long-term changes in behavior and learning abilities.