147. Effects of maternal immune activation on embryonic hypothalamic development

Abstract

Maternal infection has been linked to disorders such as autism, anxiety, cerebral palsy, and schizophrenia in the offspring children. Recent research suggests that an inflammatory immune response mounted by the mother may alter the fetal environment and disrupt normal developmental processes. It has been previously shown that increased inflammatory cytokine levels in fetal brains, as seen during maternal inflammation, can affect the timing of neuronal differentiation and survival, thereby providing a potential link between maternal inflammation, fetal neurodevelopment, and the onset of disorders during childhood. Here we seek to explore whether maternal inflammation causes changes in hypothalamic development, a key region known to contribute to various disorders. Our overarching goal is to determine whether exposure to maternal inflammation at specific periods in gestation leads to changes in the onset and/or duration of hypothalamic neurogenesis, as an entry point towards linking in utero environment with adverse health outcome in offspring. Here we examine the timing of hypothalamic neuronal birth using 5-Bromol-2′-deoxyuridine (BrdU) labeling to determine whether neurogenesis or gliogenesis is affected in embryos by onset of maternal inflammation induced by lipopolysaccharide (LPS) during key windows of development. Recently, we have looked for alternations in neuronal birth following onset of embryonic hypothalamic neurogenesis in pups born of dams treated with LPS. This exposed whether hypothalamic development in fetal brains was perturbed after induction of maternal inflammation.