title: Selective contributions of neuronal and astroglial interleukin-1 receptor 1 to the regulation of sleep.
abstract: Interactions between sleep and immune function are bidirectional. Although the mechanisms that govern these interactions are not fully elucidated, the pro-inflammatory cytokine, interleukin-1β (IL-1), is a known regulator of sleep and mediator of immune responses. To further clarify the underlying substrates of sleep and immune interactions, we engineered two transgenic mouse lines that express interleukin-1 receptor 1 (IL1R1) only in the central nervous system (CNS) and selectively on neurons (NSE-IL1R1) or astrocytes (GFAP-IL1R1). During spontaneous sleep, compared to wild type (WT) animals, NSE-IL1R1 and GFAP-IL1R1 mice have more rapid eye movement sleep (REMS) that is characterized by reduced theta power in the electroencephalogram (EEG) spectra. The non-REM sleep (NREMS) EEG of each of the IL1R1 transgenic mouse strains also is characterized by enhanced power in the delta frequency band. In response to 6h of sleep deprivation, sleep of both IL1R1 transgenic mouse strains is more consolidated than that of WT animals. Additionally, the NREMS EEG of NSE-IL1R1 mice contains less delta power after sleep deprivation, suggesting astroglial IL1R1 activity may modulate sleep homeostasis. Intracerebroventricular injection of IL-1 fails to alter sleep or brain temperature of NSE-IL1R1 or GFAP-IL1R1 mice. These data suggest that selective IL1R1 expression on neurons or on astrocytes is not sufficient for centrally-administered IL-1 to induce sleep or fever. Lack of sleep and febrile responses to IL-1 in these IL1R1 transgenic mouse strains may be due to their inability to produce IL-6 in brain. Overall, these studies demonstrate, through the use of novel transgenic mice, that IL1R1 on neurons and astrocytes differentially mediates aspects of sleep under physiological conditions and in response to central IL-1 administration.
authors: Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, United States; Program in Biomedical Sciences, University of Michigan, Ann Arbor, MI, United States; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States.
authors: Ashley M
authors: AM
authors: Ingiosi
authors: Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States.
authors: Richard M
authors: RM
authors: Raymond
authors: Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States.
authors: Maria N
authors: MN
authors: Pavlova
authors: Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States; Program of Neurobiology and Behavior, University of Washington, Seattle, WA, United States. Electronic address: mopp@uw.edu.
authors: Mark R
authors: MR
authors: Opp
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D004569:Electroencephalography; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D017472:Receptors, Interleukin-1
keywords: Astrocyte; Cytokine; Fever; IL-1; IL-6; Neuron; Sleep