Platelet‐activating factor receptor‐deficient mice are protected from experimental sleep apnea‐induced learning deficits

It is reported that mice deficient in the cell surface receptor for PAF (PAFR–/–), a bioactive mediator of oxidative stress and inflammation, are protected from the spatial reference learning deficits associated with IH, and indicates that inflammatory signaling and neurobehavioral impairments induced by IH are mediated through PAF receptors.

Abstract

Intermittent hypoxia (IH) during sleep, a hallmark of sleep apnea, is associated with neurobehavioral impairments, regional neurodegeneration and increased oxidative stress and inflammation in rodents. Platelet-activating factor (PAF) is an important mediator of both normal neural plasticity and brain injury. We report that mice deficient in the cell surface receptor for PAF (PAFR-/-), a bioactive mediator of oxidative stress and inflammation, are protected from the spatial reference learning deficits associated with IH. Furthermore, PAFR-/- exhibit attenuated elevations in inflammatory signaling (cyclo-oxygenase-2 and inducible nitric oxide synthase activities), degradation of the ubiquitin-proteasome pathway and apoptosis observed in wild-type littermates (PAFR+/+) exposed to IH. Collectively, these findings indicate that inflammatory signaling and neurobehavioral impairments induced by IH are mediated through PAF receptors.