Obstructive sleep apnea (OSA) affects over 2% of the adult population in the United states and is associated with significant neurobehavioral and cardiovascular morbidities. The morbidities of OSA relate at least in part to sleep fragmentation and intermittent hypoxia, both consequences of sleep- related collapse of the upper airway. In humans with OSA, there is significant variance in the manifestation of both the neurobehavioral and cardiovascular consequences. This variance in morbidity is only partially explained by the severity of disease. These investigators believe that vulnerability tot he morbidities of OSA is, in part, genetically-determined. For this proposal, they will focus on the substantial neurobehavioral consequences of sleep apnea. To begin to determine the genetic mechanisms contributing to the differential vulnerabilities, they will look separately at sleep fragmentation and chronic intermittent hypoxia (CIH) responses in inbred strains of mice. They will first expand the phenotypical response to sleep disruption to include, not only electroencephalographic changes, but also to characterize the neurobehavioral responses: sleepiness, changes in motor activity, learning, short and long term memory, vigilance and recovery for each of these parameters following exposure to sleep fragmentation or CIH. Responses to CIH will be characterized in the same manner. A high throughput screening algorithm will be validated against the full phenotypic responses to detect not only mutant sleep responses but mutant neurobehavioral responses characteristic of OSA. Therefore, this work provides an essential foundation for determining gene function in the susceptibility of sleepiness, impaired cognation and behavioral responses caused by obstructive sleep apnea. (End of Abstract.)

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL065225-03
Application #
6527562
Study Section
Special Emphasis Panel (ZHL1-CSR-L (M1))
Program Officer
Twery, Michael
Project Start
2000-09-30
Project End
2004-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
3
Fiscal Year
2002
Total Cost
$237,750
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Veasey, Sigrid Carlen (2006) Obstructive sleep apnea: re-evaluating our index of severity. Sleep Med 7:5-6
Sanfilippo-Cohn, Benjamin; Lai, Saien; Zhan, Guanxia et al. (2006) Sex differences in susceptibility to oxidative injury and sleepiness from intermittent hypoxia. Sleep 29:152-9
Zhan, Guanxia; Serrano, Faridis; Fenik, Polina et al. (2005) NADPH oxidase mediates hypersomnolence and brain oxidative injury in a murine model of sleep apnea. Am J Respir Crit Care Med 172:921-9
Zhan, Guanxia; Fenik, Polina; Pratico, Domenico et al. (2005) Inducible nitric oxide synthase in long-term intermittent hypoxia: hypersomnolence and brain injury. Am J Respir Crit Care Med 171:1414-20
Veasey, Sigrid C; Yeou-Jey, Hsu; Thayer, Peter et al. (2004) Murine Multiple Sleep Latency Test: phenotyping sleep propensity in mice. Sleep 27:388-93
Veasey, Sigrid C; Davis, Christine W; Fenik, Polina et al. (2004) Long-term intermittent hypoxia in mice: protracted hypersomnolence with oxidative injury to sleep-wake brain regions. Sleep 27:194-201