Prevention of apnea-induced apoptosis in NREM- and REM-generating nuclei of adult guinea pigs

Abstract The present study was designed to investigate the effects of recurrent periods of apnea/hypoxia on the morphology of neurons in sites that control NREM and REM sleep. In addition, we determined whether the administration of a GABA agonist, eszopiclone, was capable of preventing the degenerative, i.e., apoptotic, sequelae of hypoxia in these sleep-promoting neurons. Adult guinea pigs were divided into control (normoxic) and hypoxic groups; a separate group of hypoxic animals was administered eszopiclone. Recurrent periods of hypoxia and normoxia lasted for a duration of 3 h. Subsequently, the brains were sectioned, and areas in the CNS that control NREM sleep as well as REM sleep were examined after staining with an antibody raised against single-stranded DNA, which labels apoptotic neurons. In the group of control (normoxic) animals, apoptotic neurons were not observed in CNS regions that control NREM or REM sleep. In hypoxic animals, a large number of apoptotic neurons were found in the preceding regions. In the hypoxic animals that were administered eszopiclone, there were almost no apoptotic neurons in the brain regions that control NREM or REM sleep. These results demonstrate that recurrent periods of apnea induce extensive apoptosis in CNS nuclei that control NREM and REM sleep and that eszopiclone is capable of preventing neuronal degeneration in these sites. We suggest that the degeneration of neurons in sites that control the states of sleep is responsible for those sleep disturbances that arise as a consequence of hypoxia in individuals with sleep-related breathing disorders.