Obstructive sleep apnea (OSA) is a common sleep disorder characterized by collapse of the upper airway during sleep, leading to periods of hypoxemia which are terminated by brief arousals from sleep and reestablishment of a patent airway. Thus, the primary characteristics of OSA, intermittent hypoxia and sleep fragmentation, are thought to lead to a variety of symptoms, including daytime sleepiness and various cognitive/attentional impairments. However, despite the prevalence and severity of OSA, it remains unknown which consequences are attributable to the sleep interruption (SI) and which to intermittent hypoxia (IH). We thus here propose to take advantage of a rat model in which the effects of SI and IH can be separated. We specifically hypothesize that the SI associated with OSA, but not IH, is primarily responsible for the symptom of daytime sleepiness seen in OSA, and that this is mediated by adenosine lAD) effects, both acutely and chronically. We further hypothesize that the learning and memory impairments observed in patients with OSA are largely the result of chronic IH, acting via cell injury/apoptosis in cortical & hippocampal (HIPP) areas involved in cognitive functions. Different groups of rats will be treated with regimens of either chronic IH, or chronic SI, in order to determine the effect of these two conditions on sleepwakefulness, and on behavioral performance using a battery of tests assessing motor ability, learning & memory, and vigilance/attention. In addition, several neurobiological measures known to vary in response to either acute total sleep deprivation, or intermittent hypoxia exposure will be investigated. These measures include: adenosine levels & adenosine receptors both of which are thought to be biochemical correlates of sleepiness; apoptosis; brain glycogen previously shown to be depleted following acute sleep deprivation; and finally, changes in the electrical activity of neurons using in vitro slice preparations of the hippocampus and basal forebrain. Understanding the neurobiological mechanisms underlying the symptoms of OSA will further the targeted development of therapies to treat, and/or to prevent, the symptoms of OSA.
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