Chronic intermittent hypoxia causes oligodendrocyte lineage cell dysfunction and cognitive deficits in a murine model: Partial reversal by reoxygenation treatment.

Abstract

Obstructive Sleep Apnea (OSA) is a common sleep-related respiratory disorder characterized by chronic intermittent hypoxia (CIH). However, the impact of and mechanisms underlying CIH on cognitive function remain unclear. We herein used a mouse model that mimics the hypoxic conditions observed in patients with moderate to severe OSA, and analyzed the effects of CIH exposure on cognition as well as the possible underlying mechanisms. Additionally, we examined the effects of reoxygenation treatment on CIH-induced cognitive impairments. Our findings demonstrate that CIH exposure extensively impairs cognitive function, as evidenced by the poor performance of the mice in multiple behavioral assessments of learning and memory. Mice exposed to CIH exhibited reduced myelin density, accompanied by decreased branching of oligodendrocyte precursor cells (OPCs), as well as reduced numbers of OPCs and oligodendrocytes. We further revealed that CIH impaired myelin plasticity, which may be linked to hyperactivated autophagy in these cells. Furthermore, CIH exposure caused synapse loss and altered neuronal autophagy. Notably, reoxygenation treatment partially rescued the cognitive deficits induced by CIH exposure. In conclusion, CIH causes cognitive deficits and suppresses myelin plasticity, which may be linked to overactivation of autophagy in OPCs. Reoxygenation only partially rescues the CIH-caused cognitive deficits.