ASTROCYTE-MEDIATED REGULATION OF PH-DEPENDENT RESPIRATORY HOMEOSTASIS

Neonatal apnea remains a common clinical problem, despite decades of research. Increasing evidence suggests that astrocytes play an active role in respiratory regulation, particularly through their ability to sense extracellular pH and CO₂ changes and to modulate neuronal networks and their electrophysiological activity via ATP release. However, it remains unknown whether astrocytes possess an intrinsic, developmentally programmed mechanisms that determine their sensitivity to hypoxic–acidotic challenges after birth. Here, we address this gap by testing the hypothesis that environmental conditions during astrocyte differentiation affect astrocyte–neuron interactions and neuronal electrophysiological responses to hypoxia and pH drop upon maturation. Using controlled in vitro human and rat models, we investigated whether astrocyte preconditioning can either protect neuronal network activity or exacerbate hypoxic failure. The preliminary results indicate that neurons rapidly respond to acute hypoxia and that astrocyte phenotypes may regulate the level of this response. Our research is expected to provide new insight into the role of astrocytes and fetal environmental factors, such as hypoxia or inflammatory activation, in the risk of neonatal apnea, and into how these factors impact neuronal function.