title: Vagotomy attenuates brain cytokines and sleep induced by peripherally administered tumor necrosis factor-α and lipopolysaccharide in mice.
abstract: OBJECTIVE
  Systemic tumor necrosis factor-α (TNF-α) is linked to sleep and sleep altering pathologies in humans. Evidence from animals indicates that systemic and brain TNF-α have a role in regulating sleep. In animals, TNF-α or lipopolysaccharide (LPS) enhance brain pro-inflammatory cytokine expression and sleep after central or peripheral administration. Vagotomy blocks enhanced sleep induced by systemic TNF-α and LPS in rats, suggesting that vagal afferent stimulation by TNF-α enhances pro-inflammatory cytokines in sleep-related brain areas. However, the effects of systemic TNF-α on brain cytokine expression and mouse sleep remain unknown.
  
  
  METHODS
  We investigated the role of vagal afferents on brain cytokines and sleep after systemically applied TNF-α or LPS in mice.
  
  
  RESULTS
  Spontaneous sleep was similar in vagotomized and sham-operated controls. Vagotomy attenuated TNF-α- and LPS-enhanced non-rapid eye movement sleep (NREMS); these effects were more evident after lower doses of these substances. Vagotomy did not affect rapid eye movement sleep responses to these substances. NREMS electroencephalogram delta power (0.5-4 Hz range) was suppressed after peripheral TNF-α or LPS injections, although vagotomy did not affect these responses. Compared to sham-operated controls, vagotomy did not affect liver cytokines. However, vagotomy attenuated interleukin-1 beta (IL-1β) and TNF-α mRNA brain levels after TNF-α, but not after LPS, compared to the sham-operated controls.
  
  
  CONCLUSIONS
  We conclude that vagal afferents mediate peripheral TNF-α-induced brain TNF-α and IL-1β mRNA expressions to affect sleep. We also conclude that vagal afferents alter sleep induced by peripheral pro-inflammatory stimuli in mice similar to those occurring in other species.
authors.affiliation: Sleep and Performance Research Center, Washington State University, Spokane, WA 99210-1495, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Zielinski
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Dunbrasky
authors.forename: Ping
authors.initials: P
authors.lastname: Taishi
authors.forename: Gianne
authors.initials: G
authors.lastname: Souza
authors.forename: James M
authors.initials: JM
authors.lastname: Krueger
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D016207:Cytokines / Q000032:analysis* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017286:Polysomnography; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology; D014628:Vagotomy / Q000379:methods; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha
keywords: EEG; Vagotomy; interleukin-1β; lipopolysaccharide; mouse; sleep; tumor necrosis factor-α; vagal afferents
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