title: The neuron-specific interleukin-1 receptor accessory protein is required for homeostatic sleep and sleep responses to influenza viral challenge in mice.
abstract: Interleukin-1β (IL1) is involved in sleep regulation and sleep responses induced by influenza virus. The IL1 receptor accessory protein (AcP) and an alternatively spliced isoform of AcP found primarily in neurons, AcPb, form part of the IL1 signaling complex. IL1-induced sleep responses depend on injection time. In rat cortex, both IL1 mRNA and AcPb mRNA peak at Zeitgeber Time (ZT) 0 then decline over the daylight hours. Sleep deprivation enhances cortical IL1 mRNA and AcPb mRNA levels, but not AcP mRNA. We used wild type (WT) and AcPb knockout (KO) mice and performed sleep deprivation between ZT10 and 20 or between ZT22 and 8 based on the time of day expression profiles of AcPb and IL1. We hypothesized that the magnitude of the responses to sleep loss would be strain- and time of day-dependent. In WT mice, NREMS and REMS rebounds occurred regardless of when they were deprived of sleep. In contrast, when AcPbKO mice were sleep deprived from ZT10 to 20 NREMS and REMS rebounds were absent. The AcPbKO mice expressed sleep rebound if sleep loss occurred from ZT22 to 8 although the NREMS responses were not as robust as those that occurred in WT mice. We also challenged mice with intranasal H1N1 influenza virus. WT mice exhibited the expected enhanced sleep responses. In contrast, the AcPbKO mice had less sleep after influenza challenge compared to their own baseline values and compared to WT mice. Body temperature and locomotor activity responses after viral challenge were lower and mortality was higher in AcPbKO than in WT mice. We conclude that neuron-specific AcPb plays a critical role in host defenses and sleep homeostasis.
authors.affiliation: College of Medical Sciences and the Sleep and Performance Research Center, Washington State University Spokane, Spokane, WA 99210, United States. Electronic address: cjdavis@wsu.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Davis
authors.affiliation: College of Medical Sciences and the Sleep and Performance Research Center, Washington State University Spokane, Spokane, WA 99210, United States.
authors.forename: Danielle
authors.initials: D
authors.lastname: Dunbrasky
authors.affiliation: College of Medical Sciences and the Sleep and Performance Research Center, Washington State University Spokane, Spokane, WA 99210, United States.
authors.forename: Marcella
authors.initials: M
authors.lastname: Oonk
authors.affiliation: College of Medical Sciences and the Sleep and Performance Research Center, Washington State University Spokane, Spokane, WA 99210, United States.
authors.forename: Ping
authors.initials: P
authors.lastname: Taishi
authors.affiliation: Department of Anesthesiology & Pain Medicine, University of Washington, Seattle, WA 98104, United States.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Opp
authors.affiliation: College of Medical Sciences and the Sleep and Performance Research Center, Washington State University Spokane, Spokane, WA 99210, United States.
authors.forename: James M
authors.initials: JM
authors.lastname: Krueger
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000276:immunology / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism / Q000821:virology; D006706:Homeostasis / Q000276:immunology / Q000502:physiology*; D053118:Influenza A Virus, H1N1 Subtype; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000276:immunology / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000821:virology; D012890:Sleep / Q000276:immunology / Q000502:physiology*; D012892:Sleep Deprivation / Q000378:metabolism* / Q000821:virology
chemical_list: D053577:Interleukin-1 Receptor Accessory Protein
keywords: Cytokine; H1N1; Mouse; PR8; Recuperation; Sleep deprivation