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Abstract: Obstructive sleep apnea and other sleep-related breathing disorders result in recurrent periods of oxygen deprivation (hypoxia), hypercapnia and an increase in the cellular production of reactive oxygen species (oxidative stress-related injury). Individuals with these disorders suffer from a variety of cellular abnormalities that result in cardiopulmonary dysfunctions, disturbances in sleep and other pathologies. In the present experiment, using an animal model of sleep apnea, we determined that the degeneration of neurons and glia, due to apoptosis, occurs in specific regions of the pons and medulla. Adult guinea pigs, which were divided into control (normoxic) and experimental (hypoxic) groups, were anesthetized with α-chloralose and immobilized with Flaxedil. Apnea (hypoxia) was induced by ventilatory arrest in order to desaturate the oxyhemoglobin to 75% SpO2. A sequence of apnea, followed by ventilation with recovery to >95% SpO2, was repeated for a period of 3h. At the end of the period of recurrent apnea, the animals were perfused and brain sections were immunostained with a mouse monoclonal antibody raised against single-stranded DNA (ssDNA). Apoptotic neurons and glia, which were not found in the control group of animals, were present in brainstem regions in hypoxic group of animals; these regions involved in the control of respiration (e.g., the parafacial respiratory group and the ventral respiratory group), cardiovascular functions (e.g., the nucleus ambiguus, the nucleus tractus solitarius and the dorsal motor nucleus of the vagus) as well as REM sleep (the nucleus pontis oralis) and wakefulness (e.g., the dorsal raphe and locus ceruleus). We suggest apoptotic neurons and glia in critical areas of the pons and medulla results in many of the comorbidities experienced by patients with sleep-disordered breathing pathologies. [ABSTRACT FROM AUTHOR]

Abstract: Obstructive sleep apnea (OSA) and sleep-disordered breathing (SDB) can result in impaired cognition and mental acuity, and the generation of mood disorders, including depression. However, the mechanisms of neuronal damage for these complications have not been elucidated. Accordingly, using immunohistochemical technique with monoclonal antibody against single-stranded DNA, we examined the morphological effects of chronic recurrent apnea on neurons in the hippocampus and related forebrain sites in guinea pigs. Our results show that a large number of neurons labeled by anti-ssDNA antibody were present in the cingulate, insular and frontal cortices, the hippocampus and the amygdala in conjunction with periods of recurrent apnea. However, no labeling was observed in comparable regions of the brain in control guinea pigs. In the cortices of experimental animals, labeled neurons were detected mainly in the superficial layers (II–III) in the frontal, insular and cingulate cortex. In the hippocampus, most labeled neurons were located in the CA1 region, in which most of stained neurons were observed in strata pyramidal, while only a few positive neurons were located in the strata radiatum and the strata oriens. In addition, a large number of labeled neurons were also detected in the central nucleus of amygdala in the guinea pigs underwent recurrent periods of apnea. The present data indicate that recurrent apnea results in cell death in the hippocampus and related forebrain regions via mechanisms of apoptosis, which may represent the basis for the clinical complications of obstructive sleep apnea and sleep-disordered breathing. [Copyright &y& Elsevier]