title: Cell injury and repair resulting from sleep loss and sleep recovery in laboratory rats.
abstract: OBJECTIVE
  Increased cell injury would provide the type of change in constitution that would underlie sleep disruption as a risk factor for multiple diseases. The current study was undertaken to investigate cell injury and altered cell fate as consequences of sleep deprivation, which were predicted from systemic clues.
  
  
  METHODS
  Partial (35% sleep reduction) and total sleep deprivation were produced in rats for 10 days, which was tolerated and without overtly deteriorated health. Recovery rats were similarly sleep deprived for 10 days, then allowed undisturbed sleep for 2 days. The plasma, liver, lung, intestine, heart, and spleen were analyzed and compared to control values for damage to DNA, proteins, and lipids; apoptotic cell signaling and death; cell proliferation; and concentrations of glutathione peroxidase and catalase.
  
  
  RESULTS
  Oxidative DNA damage in totally sleep deprived rats was 139% of control values, with organ-specific effects in the liver (247%), lung (166%), and small intestine (145%). Overall and organ-specific DNA damage was also increased in partially sleep deprived rats. In the intestinal epithelium, total sleep deprivation resulted in 5.3-fold increases in dying cells and 1.5-fold increases in proliferating cells, compared with control. Recovery sleep restored the balance between DNA damage and repair, and resulted in normal or below-normal metabolic burdens and oxidative damage.
  
  
  CONCLUSIONS
  These findings provide physical evidence that sleep loss causes cell damage, and in a manner expected to predispose to replication errors and metabolic abnormalities; thereby providing linkage between sleep loss and disease risk observed in epidemiological findings. Properties of recovery sleep include biochemical and molecular events that restore balance and decrease cell injury.
authors.affiliation: Department of Neurology, The Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Everson
authors.affiliation: Department of Neurology, The Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Henchen
authors.affiliation: Department of Population Health, The Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Aniko
authors.initials: A
authors.lastname: Szabo
authors.affiliation: Department of Biophysics, The Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Neil
authors.initials: N
authors.lastname: Hogg
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D016923:Cell Death; D049109:Cell Proliferation; D004249:DNA Damage; D004260:DNA Repair; D004198:Disease Susceptibility; D005979:Glutathione Peroxidase / Q000378:metabolism; D007421:Intestine, Small; D008099:Liver; D008168:Lung; D008297:Male; D009928:Organ Specificity; D018384:Oxidative Stress; D051381:Rats; D015398:Signal Transduction; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000150:complications / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000975:Antioxidants; D002374:Catalase; D005979:Glutathione Peroxidase
keywords: 8-hydroxydeoxyguanosine; apoptosis; cell injury; lipid peroxidation; oxidative stress