Vagotomy attenuates brain cytokines and sleep induced by peripherally administered tumor necrosis factor-α and lipopolysaccharide in mice

Systemic tumor necrosis factor-α (TNF-α) is linked to sleep and sleep altering pathologies in humans. Evidence from animals indicates that systemic and brain TNF-α have a role in regulating sleep. In animals, TNF-α or lipopolysaccharide (LPS) enhance brain pro-inflammatory cytokine expression and sl...

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Bibliographic Details
Published in:	Sleep (New York, N.Y.) Vol. 36; no. 8; pp. 1227 - 1238
Main Authors:	Zielinski, Mark R, Dunbrasky, Danielle L, Taishi, Ping, Souza, Gianne, Krueger, James M
Format:	Journal Article
Language:	English
Published:	United States Associated Professional Sleep Societies, LLC 01-08-2013
Subjects:	Animals Brain Chemistry - drug effects Brain Chemistry - physiology Cytokines - analysis Cytokines - physiology Dose-Response Relationship, Drug Gene Expression - drug effects Gene Expression - physiology Lipopolysaccharides - pharmacology Male Mice Mice, Inbred C57BL Polysomnography Sleep - drug effects Sleep - physiology Sleep Stages - drug effects Sleep Stages - physiology Tumor Necrosis Factor-alpha - pharmacology Tumor Necrosis Factor-alpha - physiology Vagotomy - methods Vagotomy Attenuates Brain Cytokines and Effects on Sleep in Mice Vagus Nerve - physiology sleep mouse vagal afferents EEG tumor necrosis factor-α lipopolysaccharide Vagotomy interleukin-1β
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Summary:	Systemic tumor necrosis factor-α (TNF-α) is linked to sleep and sleep altering pathologies in humans. Evidence from animals indicates that systemic and brain TNF-α have a role in regulating sleep. In animals, TNF-α or lipopolysaccharide (LPS) enhance brain pro-inflammatory cytokine expression and sleep after central or peripheral administration. Vagotomy blocks enhanced sleep induced by systemic TNF-α and LPS in rats, suggesting that vagal afferent stimulation by TNF-α enhances pro-inflammatory cytokines in sleep-related brain areas. However, the effects of systemic TNF-α on brain cytokine expression and mouse sleep remain unknown. We investigated the role of vagal afferents on brain cytokines and sleep after systemically applied TNF-α or LPS in mice. Spontaneous sleep was similar in vagotomized and sham-operated controls. Vagotomy attenuated TNF-α- and LPS-enhanced non-rapid eye movement sleep (NREMS); these effects were more evident after lower doses of these substances. Vagotomy did not affect rapid eye movement sleep responses to these substances. NREMS electroencephalogram delta power (0.5-4 Hz range) was suppressed after peripheral TNF-α or LPS injections, although vagotomy did not affect these responses. Compared to sham-operated controls, vagotomy did not affect liver cytokines. However, vagotomy attenuated interleukin-1 beta (IL-1β) and TNF-α mRNA brain levels after TNF-α, but not after LPS, compared to the sham-operated controls. We conclude that vagal afferents mediate peripheral TNF-α-induced brain TNF-α and IL-1β mRNA expressions to affect sleep. We also conclude that vagal afferents alter sleep induced by peripheral pro-inflammatory stimuli in mice similar to those occurring in other species.
ISSN:	0161-8105 1550-9109
DOI:	10.5665/sleep.2892