Obstructive sleep apnea syndrome (OSAS) is a frequent condition affecting up to 5 percent of the population, and is characterized by repeated episodes of hypoxia and recurrent EEG/behavioral arousal, particularly during REM sleep. When untreated, OSAS is associated with significant neurocognitive morbidities such as excessive daytime sleepiness and diminished intellectual performance, attention span, learning and vigilance. Although some experimental evidence suggest that chronic continuous hypoxia (CCH) may elicit neural dysfunction, the relative contributions of episodic hypoxia to OSAS-associated neurocognitive dysfunction remain unclear. In a rat model, regional differences in susceptibility of the hippocampal formation to chronic intermittent hypoxia (CIH) emerged. The CA1 region of the hippocampus displayed major increases in apoptosis and anatomical disruption while the CA3 hippocampal region was unaffected. Similarly, c-Fos protein was markedly enhanced in CA1 but not in CA3. Recent developments in 2-dimensional electrophoresis, mass spectroscopy, and bioinformatics permit the large scale analysis of proteins, termed proteomics. To test the hypothesis that a restricted number of identifiable proteins accounts for the differential susceptibility of the CA1 and CA3 regions of the hippocampus to CIH, the project proposes to examine the following specific aims: (1) To characterize the protein expression patterns of CA1 and CA3 regions of the hippocampus in the adult rat, by establishing a proteomic database of these 2 regions; (2) To determine differences in temporal changes of protein expression between the CA1 and CA3 regions of the hippocampus in adult rats exposed to CIH by comparing the changes in the proteomic databases within each region; (3) To determine differences in temporal changes of protein expression between the CA1 and CA3 regions of the hippocampus in adult rats exposed to CCH by comparing proteomic datasets established during CCH. In addition, differential proteomic analysis will be conducted between CCH and CIH. These studies will characterize changes in protein expression and post-translational modifications that may have important implications for cell survival and/or adaption to intermittent and sustained hypoxia.
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