The role of reactive oxygen species in cognitive impairment associated with sleep apnea.

Abstract

Obstructive sleep apnea (OSA), a common breathing and sleeping disorder, is associated with a broad range of neurocognitive difficulties. Intermittent hypoxia (IH), one major characteristic of OSA, has been shown to impair learning and memory due to increased levels of reactive oxygen species (ROS). Under normal conditions, ROS are produced in low concentrations and act as signaling molecules in different processes. However, IH treatment leads to elevated ROS production via multiple pathways, including mitochondrial electron transport chain dysfunction and in particular complex I dysfunction, and induces oxidative tissue damage. Moreover, elevated ROS results in the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) and increased activity of peroxisomes, such as NADPH oxidase, xanthine oxidase and phospholipase A2. Furthermore, oxidative tissue damage has been found in regions of the brains of patients with OSA, including the cortex and hippocampus, which are associated with memory and executive function. Furthermore, increased ROS levels in these regions of the brain induce damage via inflammation, apoptosis, ER stress and neuronal activity disturbance. The present review focuses on the mechanism of excessive ROS production in an OSA model and the relationship between ROS and cognitive impairment.