Exposure to chronic intermittent hypoxia (CIH), such as encountered in obstructive sleep apnea (OSA), is associated with substantial neurocognitive morbidity. The primary objective of this proposal is to determine the neurobehavioral consequences of exposure to CIH in the developing rat and the effects of this stressor on neural pathways involved in the stress response. Developing rats (PN10), will be group-housed with their dam in custom-made environmental chambers in which O2 concentration will continuously be measured by an O2 analyzer, and an intermittent hypoxia profile consisting of alternating 90 second epochs of hypoxia (10 percentO2) and room air will be applied for 14-days during habitual sleep times, with minimal disruption of sleep architecture. Learning and memory in the Morris water maze will be assessed at 0, 24 and 60 days of age following exposure to CIH in order to determine the effects of CIH exposure during development on cognitive function. Additionally, in situ hydridization detection of CRH and glucocorticoid receptor mRNA expression will be determined at 0, 24, and 60 days of age following exposure to CIH to determine the effects on neural pathways involved in responses to stress. These studies will provide unique insights into the effect of CIH on learning and memory. More importantly, these experiments will provide information on the long-term consequences of exposure to CIH during development and generate the foundation for clinical studies of OSAS in children.
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