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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HD042395-01
Application #
6487029
Study Section
Special Emphasis Panel (ZRG1-F02A (20))
Program Officer
Freund, Lisa S
Project Start
2002-03-01
Project End
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
1
Fiscal Year
2002
Total Cost
$36,592
Indirect Cost
Name
University of Louisville
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Louisville
State
KY
Country
United States
Zip Code
40292
Row, Barry W; Kheirandish, Leila; Cheng, Yu et al. (2007) Impaired spatial working memory and altered choline acetyltransferase (CHAT) immunoreactivity and nicotinic receptor binding in rats exposed to intermittent hypoxia during sleep. Behav Brain Res 177:308-14
Kheirandish, Leila; Gozal, David; Pequignot, Jean-Marc et al. (2005) Intermittent hypoxia during development induces long-term alterations in spatial working memory, monoamines, and dendritic branching in rat frontal cortex. Pediatr Res 58:594-9
Li, Richard C; Row, Barry W; Kheirandish, Leila et al. (2004) Nitric oxide synthase and intermittent hypoxia-induced spatial learning deficits in the rat. Neurobiol Dis 17:44-53
Gozal, David; O'Brien, Louise; Row, Barry W (2004) Consequences of snoring and sleep disordered breathing in children. Pediatr Pulmonol Suppl 26:166-8
Gozal, David; Reeves, Stephen R; Row, Barry W et al. (2003) Respiratory effects of gestational intermittent hypoxia in the developing rat. Am J Respir Crit Care Med 167:1540-7
Row, Barry W; Goldbart, Aviv; Gozal, Evelyne et al. (2003) Spatial pre-training attenuates hippocampal impairments in rats exposed to intermittent hypoxia. Neurosci Lett 339:67-71
Goldbart, A; Row, B W; Kheirandish, L et al. (2003) Intermittent hypoxic exposure during light phase induces changes in cAMP response element binding protein activity in the rat CA1 hippocampal region: water maze performance correlates. Neuroscience 122:585-90
Gozal, David; Row, Barry W; Kheirandish, Leila et al. (2003) Increased susceptibility to intermittent hypoxia in aging rats: changes in proteasomal activity, neuronal apoptosis and spatial function. J Neurochem 86:1545-52
Gozal, David; Row, Barry W; Gozal, Evelyne et al. (2003) Temporal aspects of spatial task performance during intermittent hypoxia in the rat: evidence for neurogenesis. Eur J Neurosci 18:2335-42
Row, Barry W; Liu, Rugao; Xu, Wei et al. (2003) Intermittent hypoxia is associated with oxidative stress and spatial learning deficits in the rat. Am J Respir Crit Care Med 167:1548-53

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