Retarded astrogliogenesis in response to hypoxia is facilitated by downregulation of CIRBP

Abstract

The adverse impacts of chronic hypoxia on maternal and infant health at high altitudes warrant significant attention. However, effective protective measures against the resultant growth restrictions and neurodevelopmental disorders in infants and young children are still lacking. This study investigated the neurodevelopment of mice offspring under hypoxic conditions by exposing pregnant mice to a hypobaric oxygen chamber that simulated the hypobaric hypoxia at an altitude of 4000 m until 28 days after delivery. Our findings suggested that prolonged exposure to hypoxia might result in emotional abnormalities and social disorders in offspring. The significant reduction in astrogliogenesis was a characteristic feature associated with neurodevelopmental disorders induced by hypoxia. Further studies demonstrated that cold-induced RNA-binding protein (CIRBP) was a key transcriptional regulator in astrogliogenesis, which downregulated astrocytic differentiation under hypoxia through its crosstalk with the NFIA. Our study emphasized the crucial role of CIRBP in regulating astrogliogenesis and highlighted its potential as a promising target for therapeutic interventions in neurodevelopmental disorders associated with hypoxia.

Keywords

• High altitude
• Hypoxia
• CIRBP
• Astrogliogenesis
• NFIA
• Neurodevelopmental disorders