title: TNF-α and temporal changes in sleep architecture in mice exposed to sleep fragmentation.
abstract: TNF-α plays critical roles in host-defense, sleep-wake regulation, and the pathogenesis of various disorders. Increases in the concentration of circulating TNF-α after either sleep deprivation or sleep fragmentation (SF) appear to underlie excessive daytime sleepiness in patients with sleep apnea (OSA). Following baseline recordings, mice were subjected to 15 days of SF (daily for 12 h/day from 07.00 h to 19.00 h), and sleep parameters were recorded on days1, 7 and 15. Sleep architecture and sleep propensity were assessed in both C57BL/6J and in TNF-α double receptor KO mice (TNFR KO). To further confirm the role of TNF-α, we also assessed the effect of treatment with a TNF- α neutralizing antibody in C57BL/6J mice. SF was not associated with major changes in global sleep architecture in C57BL/6J and TNFR KO mice. TNFR KO mice showed higher baseline SWS delta power. Further, following 15 days of SF, mice injected with TNF-α neutralizing antibody and TNFR KO mice showed increased EEG SWS activity. However, SWS latency, indicative of increased propensity to sleep, was only decreased in C57BL/6J, and was unaffected in TNFR KO mice as well as in C57BL/6J mice exposed to SF but treated with TNF-α neutralizing antibody. Taken together, our findings show that the excessive sleepiness incurred by recurrent arousals during sleep may be due to activation of TNF-alpha-dependent inflammatory pathways, despite the presence of preserved sleep duration and global sleep architecture.
authors.affiliation: Department of Pediatrics, Section of Pediatric Sleep Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Navita
authors.initials: N
authors.lastname: Kaushal
authors.forename: Vijay
authors.initials: V
authors.lastname: Ramesh
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D000818:Animals; D004569:Electroencephalography; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D012890:Sleep; D012893:Sleep Wake Disorders / Q000378:metabolism* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014851:Wakefulness
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha