CIRBP regulates mitochondrial respiratory function and modulates neuronal developmental abnormalities induced by perinatal hypoxia.

The Cold-inducible RNA-binding protein (CIRBP) plays a crucial role in modulating cellular responses to environmental stressors, including hypothermia, hypoxia, and ultraviolet radiation. It has been reported to have a significant impact on cognitive function. The proper functioning of mitochondrial respiration is essential for the growth and maturation of neural synapses, as well as cognitive function. However, the mechanisms underlying the role of CIRBP in promoting mitochondrial function during neurodevelopment remain elusive. In this study, we aimed to understand how pregnancy hypoxia affected and enhanced cognition in offspring using CIRBP both in vivo and in vitro. Our findings suggested that perinatal hypoxia insult may result in compromised brain development and aberrant neuron maturation within the hippocampus of P14 d mice, as well as impairment in spatial learning and memory. We provide evidence demonstrating that CIRBP regulates mitochondrial complex I by modulating the expression of Ndufb8 and influences complex V through the regulation of ATP5a. This mechanism effectively improves energy metabolism disorders and corrects the abnormal neuronal development caused by hypoxia. In summary, CIRBP exerts a protective effect against developmental delay and memory impairment induced by prenatal hypoxia through the regulation of mitochondrial function to maintain synaptic homeostasis. Our findings provide potential targets for preventing and treating brain damage resulting from hypoxic exposure during pregnancy.