Reduced HIF1a Signaling Enhances Apneas During Perinatal Development

Abstract

Immature neonatal breathing is characterized by the occurrence of periodic apneas that disrupt the breathing rhythm and cause intermittent hypoxia (IH). IH has been proposed as a factor that facilitates the development of respiratory control allowing for the transition from unstable to stable breathing rhythms where apneas no longer occur. In adults, IH increases hypoxia inducible factor 1a (HIF1a) signaling that remodels respiratory control and augments peripheral chemoreflexes. However, it is unclear whether HIF1a signaling contributes to the stabilization of immature neonatal breathing during the first days of perinatal life. To address this, we used whole body plethysmography to track perinatal development of breathing beginning at postnatal day zero (P0) in mice heterozygous for hypoxia inducible factor 1a (HIF1a+/−) and wildtype littermates (WT). At P0 we observed unstable breathing rhythms characterized by periodic apneas in both genotypes. However, in HIF1a+/− (n=4) apnea number was 50% greater and apnea duration was 172% longer when compared to the WT (n=3). Our ongoing experiments suggest that the switch to stable breathing rhythms occurs between postnatal days three and four. Our findings indicate that HIFa signaling is important to the of the neonatal breathing rhythm.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.