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.
Highlights
Sleep and wakefulness are controlled by a network of brain nuclei that interact in a complex fashion allowing for integration of homeostatic and circadian regulatory networks [1]
All mice including the tumor necrosis factor-alpha (TNF-a) double receptor KO mice (TNFR KO) mice recovered from surgery without any signs of infection
We show that TNF receptor (TNFR) KO mice as well as WT mice treated with TNF-a neutralizing antibody do not exhibit rebounds in NREM and rapid eye movement (REM) sleep as compared to WT mice subjected to sleep fragmentation (SF)
Summary
Sleep and wakefulness are controlled by a network of brain nuclei that interact in a complex fashion allowing for integration of homeostatic and circadian regulatory networks [1]. The mechanisms by which SD or SF induce pathological changes leading to excessive sleepiness (ES), cognitive deficits and obesity remain unclear. The levels of specific cytokines underlying the regulation of the inflammatory response may play a pivotal role in both sleep regulation and induction of ES. SD has been found to alter immune responses [7], and to lead to increased circulating levels of proinflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a), and C-reactive protein (CRP) [8,9], prolonged SD conditions in humans are unusual. A few studies have demonstrated association of sleep loss with next-day increase in IL-6 and TNF-a [10,11,12] and such changes in inflammatory cytokines have been proposed as mediators of pathological or experimentally-induced sleepiness in humans. SF is a much more prevalent condition, and yet the role of SF in modulating pro-inflammatory pathways remains virtually unexplored
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.