title: Sustained sleep fragmentation induces sleep homeostasis in mice.
abstract: OBJECTIVE
  Sleep fragmentation (SF) is an integral feature of sleep apnea and other prevalent sleep disorders. Although the effect of repetitive arousals on cognitive performance is well documented, the effects of long-term SF on electroencephalography (EEG) and molecular markers of sleep homeostasis remain poorly investigated. To address this question, we developed a mouse model of chronic SF and characterized its effect on EEG spectral frequencies and the expression of genes previously linked to sleep homeostasis including clock genes, heat shock proteins, and plasticity-related genes.
  
  
  METHODS
  N/A.
  
  
  METHODS
  Animal sleep research laboratory.
  
  
  METHODS
  Sixty-six C57BL6/J adult mice.
  
  
  METHODS
  Instrumental sleep disruption at a rate of 60/h during 14 days.
  
  
  RESULTS
  Locomotor activity and EEG were recorded during 14 days of SF followed by recovery for 2 days. Despite a dramatic number of arousals and decreased sleep bout duration, SF minimally reduced total quantity of sleep and did not significantly alter its circadian distribution. Spectral analysis during SF revealed a homeostatic drive for slow wave activity (SWA; 1-4 Hz) and other frequencies as well (4-40 Hz). Recordings during recovery revealed slow wave sleep consolidation and a transient rebound in SWA, and paradoxical sleep duration. The expression of selected genes was not induced following chronic SF.
  
  
  CONCLUSIONS
  Chronic SF increased sleep pressure confirming that altered quality with preserved quantity triggers core sleep homeostasis mechanisms. However, it did not induce the expression of genes induced by sleep loss, suggesting that these molecular pathways are not sustainably activated in chronic diseases involving SF.
authors.affiliation: Laboratory of Neuroenergetic and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.|Department of Neurology, University of California at San Francisco (UCSF), San Francisco, CA.
authors.forename: Maxime O
authors.initials: MO
authors.lastname: Baud
authors.affiliation: Laboratory of Neuroenergetic and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.|Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, KSA.|Centre de Neurosciences Psychiatriques, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland.
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Magistretti
authors.affiliation: Laboratory of Neuroenergetic and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.|Centre de Neurosciences Psychiatriques, Department of Psychiatry, Centre Hospitalier Universitaire Vaudois, Prilly, Switzerland.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Petit
mesh_terms: D000818:Animals; D001143:Arousal / Q000502:physiology; D002908:Chronic Disease; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D004569:Electroencephalography; D020869:Gene Expression Profiling; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D012892:Sleep Deprivation / Q000235:genetics / Q000503:physiopathology*; D012895:Sleep, REM / Q000502:physiology; D013997:Time Factors
keywords: BDNF; SWA; heat shock proteins; paradoxical sleep; sleep apneas; sleep fragmentation; slow waves; spindles