title: Evidence for neuroinflammatory and microglial changes in the cerebral response to sleep loss.
abstract: OBJECTIVE
  Sleep loss has pro-inflammatory effects, but the roles of specific cell populations in mediating these effects have not been delineated. We assessed the modulation of the electroencephalographic and molecular responses to sleep deprivation (S-DEP) by minocycline, a compound that attenuates microglial activation occurring in association with neuroinflammatory events.
  
  
  METHODS
  Laboratory rodents were subjected to assessment of sleep and wake in baseline and sleep deprived conditions.
  
  
  METHODS
  Adult male CD-1 mice (30-35 g) subjected to telemetric electroencephalography.
  
  
  METHODS
  Minocycline was administered daily. Mice were subjected to baseline data collection on the first day of minocycline administration and, on subsequent days, 2 S-DEP sessions, 1 and 3 h in duration, followed by recovery sleep. Following EEG studies, mice were euthanized either at the end of a 3 h S-DEP or as time-of day controls for sampling of brain messenger RNAs. Gene expression was measured by real-time polymerase chain reaction.
  
  
  RESULTS
  Minocycline-treated mice exhibited a reduction in time spent asleep, relative to saline-treated mice, in the 3-h interval immediately after administration. S-DEP resulted in an increase in EEG slow wave activity relative to baseline in saline-treated mice. This response to S-DEP was abolished in animals subjected to chronic minocycline administration. S-DEP suppressed the expression of the microglial-specific transcript cd11b and the neuroinflammation marker peripheral benzodiazepine receptor, in the brain at the mRNA level. Minocycline attenuated the elevation of c-fos expression by S-DEP. Brain levels of pro-inflammatory cytokine mRNAs interleukin-1β (il-1β), interleukin-6 (il-6), and tumor necrosis factor-α (tnfα) were unaffected by S-DEP, but were elevated in minocycline-treated mice relative to saline-treated mice.
  
  
  CONCLUSIONS
  The anti-neuroinflammatory agent minocycline prevents either the buildup or expression of sleep need in rodents. The molecular mechanism underlying this effect is not known, but it is not mediated by suppression of il-1β, il-6, and tnfα at the transcript level.
authors.affiliation: WWAMI Medical Education Program and Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Spokane, WA, USA. J_Wisor@wsu.edu
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Wisor
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Schmidt
authors.forename: William C
authors.initials: WC
authors.lastname: Clegern
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D001923:Brain Chemistry / Q000187:drug effects; D004569:Electroencephalography; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D008911:Minocycline / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D012892:Sleep Deprivation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D008911:Minocycline