This SCOR in Sleep Neurobiology of Sleep and Sleep Apnea is focused on understanding the pathogenesis of sleep apnea and its consequences and in improving treatment for this common disorder. It is estimated that obstructive sleep apnea affects 2-5% of middle-aged adults and produces both neurobehavioral (excessive sleepiness) and cardiovascular consequences. There are several components to the pathogenesis of the disorder. First, there are structural risk factors that reduce the size of the upper airway even in wakefulness. In Project 01 (Richard Schwab, M.D.) we argue that there several structural risk factors that are likely to have an important genetic basis. We address this in a case control study in which we also study sibs of probands and controls. Imaging techniques are used to identify intermediate traits and we week family aggregation of such traits that are not explained by shared environmental risk factors. A second component of the pathogenesis is the neural mechanism that leads to hypotonia during sleep. We propose that two brainstem systems are critical, i.e. the serotonergic and noradrenergic neurons. The former, we propose, plays a critical role in mediating the reduction in motor done during sleep, while the latter plays a large role in mediating changes in the effect of afferent inputs and hence in apnea termination. This proposed relative role of these two neural systems is addressed in Project 02 (Leszek Kubin, Ph.D), while in Project 03 (Joan C. Hendricks, V.M.D.., Ph.D.) we address whether manipulating the serotonin system will increase the motor tone of the airway and hence represent a pharmacotherapy for the disorder. While these studies address the pathogenesis of the disorder, in Project 04 (Allan I. Pack, M.D., Ph.D.) we turn our attention to arguable the most important consequence of the disorder, sleepiness. Here we propose that adenosine could play a major role and we address how adenosine levels might be controlled at a molecular level in different brain regions in relation to sleep need. In the final project of the SCOR, we address shorter-term clinical needs and address, using new technology and a concept based on assessment of efficacy, the most important management problem for this disorder, the high rates of non-adherence to therapy (Project 05; Terri E. Weaver, Ph.D., R.N.). These five projects are supported by three cores (Administrative, Computer, and Human Assessment and Biostatistics Cores).
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