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Mice lacking the TNF 55 kDa receptor fail to sleep more after TNFalpha treatment
1Department of Physiology and Biophysics, University of Tennessee, Memphis, Tennessee 38163, USA.
Abstract:
Tumor necrosis factor (TNF) is a well characterized sleep-regulatory substance. To study receptor mechanisms for the sleep-promoting effects of TNF, sleep patterns were determined in control and TNF 55 kDa receptor knock-out (TNFR-KO) mice with a B6 x 129 background after intraperitoneal injections of saline or murine TNFalpha. The TNFR-KO mice had significantly less baseline sleep than the controls. TNFalpha dose-dependently increased non-rapid eye movement sleep (NREMS) in the controls but did not influence sleep in TNFR-KO mice. Although TNFR-KO mice failed to respond to TNFalpha, they had an increase in NREMS and a decrease in rapid eye movement sleep after interleukin-1beta treatment. These results indicate that TNFalpha affects sleep via the 55 kDa receptor and provide further evidence that TNFalpha is involved in physiological sleep regulation. Current results also extend the list of species to mice in which TNFalpha and interleukin-1beta are somnogenic.
Insights
Tumor necrosis factor (TNF) regulates sleep via its 55 kDa receptor. Knock-out mice lacking this receptor showed reduced baseline sleep and no response to TNF, confirming its role in sleep.
Area of Science:
- Neuroscience
- Immunology
- Sleep Medicine
Background:
- Tumor necrosis factor (TNF) is recognized as a key regulator of sleep.
- Understanding the specific receptor pathways involved in TNF's sleep-promoting effects is crucial for elucidating its physiological role.
Purpose of the Study:
- To investigate the receptor mechanisms underlying the sleep-promoting effects of TNF.
- To determine if the 55 kDa TNF receptor mediates TNF-induced sleep.
Main Methods:
- Sleep patterns were analyzed in control mice and mice lacking the 55 kDa TNF receptor (TNFR-KO).
- Mice received intraperitoneal injections of either saline or varying doses of murine TNF-alpha.
- Responses to interleukin-1 beta were also assessed in TNFR-KO mice.
Main Results:
- TNFR-KO mice exhibited significantly lower baseline sleep duration compared to control mice.
- TNF-alpha administration dose-dependently increased non-rapid eye movement sleep (NREMS) in control mice but had no effect on TNFR-KO mice.
- Despite the lack of response to TNF-alpha, TNFR-KO mice showed increased NREMS and decreased rapid eye movement sleep following interleukin-1 beta treatment.
Conclusions:
- TNF-alpha mediates its sleep-regulatory effects through the 55 kDa receptor.
- These findings provide strong evidence for TNF-alpha's involvement in physiological sleep regulation.
- The study extends the understanding of TNF-alpha and interleukin-1 beta as somnogenic substances to the mouse model.