Hypoxia-induced apoptosis in a model of sleep apnea

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) is a condition defined by the collapse of the upper airway and cessation of respiration during sleep which in turn leads to hypoxemia and subsequent arousal from sleep to restore breathing. Rats will be exposed to either sustained hypoxia levels, similar to the oxygen environment at 3000m, or intermittent hypoxia (IH), mimicking the oxygen level abnormalities of the OSA patient. Subsequent immunohistochemical assessment of apoptosis, as well as neuroanatomical tract analysis, will be performed. After IH and SH exposure, brain areas will be examined by means of immunohistochemical procedures for evidence of apoptosis, neurogenesis and hypoxia-inducible factor 1a (HIF-1 a) expression. HIF-1a activation transcriptionally regulates the expression of numerous genes, involved in both apoptosis (caspase-3) and neuroprotection (Vascular endothelial growth factor, VEGF), whose expression will also be documented. Furthermore, the retrograde tracer Fluorogold will be placed in select regions in order to determine the efferent projections of neurons that undergo programmed cell death (apoptosis) or generation (neurogenesis). Overall, it is predicted that the biochemical and apoptotic consequences of IH will be more severe than that of SH, although cellular changes will be observed after both hypoxic exposures.