2026 Volume 63 Issue 2 Pages 56-60
Obstructive sleep apnea syndrome is associated with cognitive dysfunction, but the underlying molecular mechanisms are not yet fully understood. This study investigated the effects of intermittent hypoxia, a core pathophysiological feature of obstructive sleep apnea syndrome, on cognitive function and hippocampal gene expression in mice. Eight-week-old C57BL/6J mice were exposed for 28 days to intermittent hypoxia (alternating 10–21% oxygen in 2-minute cycles, 8 hours/day), sustained hypoxia (10% oxygen, 8 hours/day), or normoxia. Behavioral assessments and hippocampal RNA sequencing were subsequently performed. Compared with the control and sustained hypoxia groups, the intermittent hypoxia group exhibited impaired memory and learning in the passive avoidance test. RNA-seq analysis revealed intermittent hypoxia-specific downregulation of the mitochondrial genes Lars2 and Vstm2l, as well as the cell junction-related gene Hmcn1. Pathway analysis further demonstrated suppression of the KEAP1-NFE2L2 (Nrf2) antioxidant pathway specifically in the intermittent hypoxia group. These findings suggest that intermittent hypoxia induces cognitive dysfunction through impaired antioxidant defense mechanisms and mitochondrial dysfunction.
