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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32MH070156-01A1
Application #
6837508
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Curvey, Mary F
Project Start
2004-08-01
Project End
2005-06-30
Budget Start
2004-08-01
Budget End
2005-06-30
Support Year
1
Fiscal Year
2004
Total Cost
$43,813
Indirect Cost
Name
Harvard University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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Ward, Christopher P; McCoy, John G; McKenna, James T et al. (2009) Spatial learning and memory deficits following exposure to 24 h of sleep fragmentation or intermittent hypoxia in a rat model of obstructive sleep apnea. Brain Res 1294:128-37
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Christie, Michael A; Bolortuya, Yunren; Chen, Li Chao et al. (2008) Microdialysis elevation of adenosine in the basal forebrain produces vigilance impairments in the rat psychomotor vigilance task. Sleep 31:1393-8
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Tao, R; Ma, Z; McKenna, J T et al. (2006) Differential effect of orexins (hypocretins) on serotonin release in the dorsal and median raphe nuclei of freely behaving rats. Neuroscience 141:1101-5
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