Dataset Information

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

ABSTRACT:

Study objective

Systemic tumor necrosis factor-? (TNF-?) is linked to sleep and sleep altering pathologies in humans. Evidence from animals indicates that systemic and brain TNF-? have a role in regulating sleep. In animals, TNF-? or lipopolysaccharide (LPS) enhance brain pro-inflammatory cytokine expression and sleep after central or peripheral administration. Vagotomy blocks enhanced sleep induced by systemic TNF-? and LPS in rats, suggesting that vagal afferent stimulation by TNF-? enhances pro-inflammatory cytokines in sleep-related brain areas. However, the effects of systemic TNF-? on brain cytokine expression and mouse sleep remain unknown.

Design

We investigated the role of vagal afferents on brain cytokines and sleep after systemically applied TNF-? or LPS in mice.

Measurements and results

Spontaneous sleep was similar in vagotomized and sham-operated controls. Vagotomy attenuated TNF-?- 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-? 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-1?) and TNF-? mRNA brain levels after TNF-?, but not after LPS, compared to the sham-operated controls.

Conclusions

We conclude that vagal afferents mediate peripheral TNF-?-induced brain TNF-? and IL-1? 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.

SUBMITTER: Zielinski MR

PROVIDER: S-EPMC3700720 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Zielinski Mark R MR Dunbrasky Danielle L DL Taishi Ping P Souza Gianne G Krueger James M JM

Sleep 20130801 8

<h4>Study objective</h4>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 en ...[more]

PMID: 23904683

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