title: Sleep fragmentation induces cognitive deficits via nicotinamide adenine dinucleotide phosphate oxidase-dependent pathways in mouse.
abstract: BACKGROUND
  Sleep fragmentation (SF) is one of the major characteristics of sleep apnea, and has been implicated in its morbid consequences, which encompass excessive daytime sleepiness and neurocognitive impairments. We hypothesized that absence of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity is neuroprotective in SF-induced cognitive impairments.
  
  
  OBJECTIVE
  To examine whether increased NADPH oxidase activity may play a role in SF-induced central nervous system dysfunction.
  
  
  METHODS
  The effect of chronic SF during the sleep-predominant period on sleep architecture, sleep latency, spatial memory, and oxidative stress parameters was assessed in mice lacking NADPH oxidase activity (gp91phox-(/Y)) and wild-type littermates.
  
  
  RESULTS
  SF for 15 days was not associated with differences in sleep duration, sleep state distribution, or sleep latency in both gp91phox-(/Y) and control mice. However, on a standard place training task, gp91phox-(/Y) mice displayed normal learning and were protected from the spatial learning deficits observed in wild-type littermates exposed to SF. Moreover, anxiety levels were increased in wild-type mice exposed to SF, whereas no changes emerged in gp91phox-(/Y) mice. Additionally, wild-type mice, but not gp91phox-(/Y) mice, had significantly elevated NADPH oxidase gene expression and activity, and in malondialdehyde and 8-oxo-2'-deoxyguanosine levels in cortical and hippocampal lysates after SF exposures.
  
  
  CONCLUSIONS
  This work substantiates an important role for NADPH oxidase in hippocampal memory impairments induced by SF, modeling sleep apnea. Targeting NADPH oxidase, therefore, is expected to minimize hippocampal impairments from both intermittent hypoxia and SF associated with the disease.
authors.affiliation: Department of Pediatrics, Pritzker School of Medicine, University of Chicago, IL 60637, USA.
authors.forename: Deepti
authors.initials: D
authors.lastname: Nair
authors.forename: Shelley X L
authors.initials: SX
authors.lastname: Zhang
authors.forename: Vijay
authors.initials: V
authors.lastname: Ramesh
authors.forename: Fahed
authors.initials: F
authors.lastname: Hakim
authors.forename: Navita
authors.initials: N
authors.lastname: Kaushal
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D015227:Lipid Peroxidation; D008297:Male; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D012892:Sleep Deprivation / Q000150:complications* / Q000378:metabolism*
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D019255:NADPH Oxidases; D003849:Deoxyguanosine