title: In Vivo Imaging of the Central and Peripheral Effects of Sleep Deprivation and Suprachiasmatic Nuclei Lesion on PERIOD-2 Protein in Mice.
abstract: OBJECTIVE
  That sleep deprivation increases the brain expression of various clock genes has been well documented. Based on these and other findings we hypothesized that clock genes not only underlie circadian rhythm generation but are also implicated in sleep homeostasis. However, long time lags have been reported between the changes in the clock gene messenger RNA levels and their encoded proteins. It is therefore crucial to establish whether also protein levels increase within the time frame known to activate a homeostatic sleep response. We report on the central and peripheral effects of sleep deprivation on PERIOD-2 (PER2) protein both in intact and suprachiasmatic nuclei-lesioned mice.
  
  
  METHODS
  In vivo and in situ PER2 imaging during baseline, sleep deprivation, and recovery.
  
  
  METHODS
  Mouse sleep-recording facility.
  
  
  METHODS
  Per2::Luciferase knock-in mice.
  
  
  METHODS
  N/A.
  
  
  RESULTS
  Six-hour sleep deprivation increased PER2 not only in the brain but also in liver and kidney. Remarkably, the effects in the liver outlasted those observed in the brain. Within the brain the increase in PER2 concerned the cerebral cortex mainly, while leaving suprachiasmatic nuclei (SCN) levels unaffected. Against expectation, sleep deprivation did not increase PER2 in the brain of arrhythmic SCN-lesioned mice because of higher PER2 levels in baseline. In contrast, liver PER2 levels did increase in these mice similar to the sham and partially lesioned controls.
  
  
  CONCLUSIONS
  Our results stress the importance of considering both sleep-wake dependent and circadian processes when quantifying clock-gene levels. Because sleep deprivation alters PERIOD-2 in the brain as well as in the periphery, it is tempting to speculate that clock genes constitute a common pathway mediating the shared and well-known adverse effects of both chronic sleep loss and disrupted circadian rhythmicity on metabolic health.
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Curie
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Maret
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Switzerland.
authors.forename: Yann
authors.initials: Y
authors.lastname: Emmenegger
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Franken
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D055879:Gene Knock-In Techniques; D006706:Homeostasis / Q000502:physiology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism*; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology*; D013493:Suprachiasmatic Nucleus / Q000293:injuries / Q000503:physiopathology*; D014851:Wakefulness / Q000502:physiology
chemical_list: D056950:Period Circadian Proteins
keywords: Purkinje cells; bioluminescence; cerebellum; cerebral cortex; circadian; clock genes; hippocampus; homeostasis