Vagotomy Attenuates Brain Cytokines and Sleep Induced by Peripherally Administered Tumor Necrosis Factor-α and Lipopolysaccharide in Mice

Overview

Journal Sleep

Publisher Oxford University Press

Specialty Psychiatry

Date 2013 Aug 2

PMID 23904683

Citations 41

Authors

Mark R Zielinski

Danielle L Dunbrasky

Ping Taishi

Gianne Souza

James M Krueger

Affiliations

Soon will be listed here.

Abstract

Study Objective: 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.

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

Measurements And Results: 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.

Conclusions: 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.

Citing Articles

Remifentanil Ameliorates Lipopolysaccharide-Induced Neuroinflammation by Regulating the Phosphatidylinositol 3-Kinase/Serine-Threonine Protein Kinase/Hypoxia-Inducible Factor 1 Alpha Pathway.

Ozcan M, Asci H, Karabacak P, Ozden E, Imeci O, Ozmen O Pharmacol Res Perspect. 2025; 13(1):e70071.

PMID: 39898372 PMC: 11788742. DOI: 10.1002/prp2.70071.

Influence of sleep on physiological systems in atherosclerosis.

Kiss M, Cohen O, McAlpine C, Swirski F Nat Cardiovasc Res. 2024; 3(11):1284-1300.

PMID: 39528718 PMC: 11567060. DOI: 10.1038/s44161-024-00560-7.

The role of Kupffer cells in microbiota-brain communication: Sleep and fever signaling in response to lipopolysaccharide.

Szentirmai E, Buckley K, Kapas L Brain Behav Immun. 2024; 123:306-314.

PMID: 39322087 PMC: 11624080. DOI: 10.1016/j.bbi.2024.09.028.

Microglia and Sleep Disorders.

Picard K, Dolhan K, Watters J, Tremblay M Adv Neurobiol. 2024; 37:357-377.

PMID: 39207702 DOI: 10.1007/978-3-031-55529-9_20.

Cyclooxygenase-2 (COX-2)-dependent mechanisms mediate sleep responses to microbial and thermal stimuli.

Szentirmai E, Buckley K, Kapas L Brain Behav Immun. 2024; 122:325-338.

PMID: 39134184 PMC: 11402559. DOI: 10.1016/j.bbi.2024.08.014.

References

KAPAS L, Hansen M, Chang H, Krueger J . Vagotomy attenuates but does not prevent the somnogenic and febrile effects of lipopolysaccharide in rats. Am J Physiol. 1998; 274(2):R406-11. DOI: 10.1152/ajpregu.1998.274.2.R406. View

Chennaoui M, Sauvet F, Drogou C, Van Beers P, Langrume C, Guillard M . Effect of one night of sleep loss on changes in tumor necrosis factor alpha (TNF-α) levels in healthy men. Cytokine. 2011; 56(2):318-24. DOI: 10.1016/j.cyto.2011.06.002. View

Floyd R, Krueger J . Diurnal variation of TNF alpha in the rat brain. Neuroreport. 1997; 8(4):915-8. DOI: 10.1097/00001756-199703030-00020. View

Vgontzas A, Papanicolaou D, Bixler E, Kales A, Tyson K, Chrousos G . Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab. 1997; 82(5):1313-6. DOI: 10.1210/jcem.82.5.3950. View

Bhushan B, Guleria R, Misra A, Luthra K, Vikram N . TNF-alpha gene polymorphism and TNF-alpha levels in obese Asian Indians with obstructive sleep apnea. Respir Med. 2008; 103(3):386-92. DOI: 10.1016/j.rmed.2008.10.001. View

Krueger J, Rector D, Churchill L . SLEEP AND CYTOKINES. Sleep Med Clin. 2011; 2(2):161-169. PMC: 2605347. DOI: 10.1016/j.jsmc.2007.03.003. View

Banks W, Robinson S . Minimal penetration of lipopolysaccharide across the murine blood-brain barrier. Brain Behav Immun. 2009; 24(1):102-9. PMC: 2789209. DOI: 10.1016/j.bbi.2009.09.001. View

Nakanishi-Minami T, Kishida K, Funahashi T, Shimomura I . Sleep-wake cycle irregularities in type 2 diabetics. Diabetol Metab Syndr. 2012; 4(1):18. PMC: 3406980. DOI: 10.1186/1758-5996-4-18. View

Ramesh V, Nair D, Zhang S, Hakim F, Kaushal N, Kayali F . Disrupted sleep without sleep curtailment induces sleepiness and cognitive dysfunction via the tumor necrosis factor-α pathway. J Neuroinflammation. 2012; 9:91. PMC: 3411474. DOI: 10.1186/1742-2094-9-91. View

10.

Ganong W . Circumventricular organs: definition and role in the regulation of endocrine and autonomic function. Clin Exp Pharmacol Physiol. 2000; 27(5-6):422-7. DOI: 10.1046/j.1440-1681.2000.03259.x. View

11.

Jakubcakova V, Flachskamm C, Deussing J, Kimura M . Deficiency of corticotropin-releasing hormone type-2 receptor alters sleep responses to bacterial lipopolysaccharide in mice. Brain Behav Immun. 2011; 25(8):1626-36. DOI: 10.1016/j.bbi.2011.06.008. View

12.

Breder C, Hazuka C, Ghayur T, Klug C, Huginin M, Yasuda K . Regional induction of tumor necrosis factor alpha expression in the mouse brain after systemic lipopolysaccharide administration. Proc Natl Acad Sci U S A. 1994; 91(24):11393-7. PMC: 45237. DOI: 10.1073/pnas.91.24.11393. View

13.

Yehuda S, Sredni B, Carasso R, Kenigsbuch-Sredni D . REM sleep deprivation in rats results in inflammation and interleukin-17 elevation. J Interferon Cytokine Res. 2009; 29(7):393-8. DOI: 10.1089/jir.2008.0080. View

14.

Rosas-Ballina M, Tracey K . Cholinergic control of inflammation. J Intern Med. 2009; 265(6):663-79. PMC: 4540232. DOI: 10.1111/j.1365-2796.2009.02098.x. View

15.

Smith G, Jerome C, Cushin B, Eterno R, Simansky K . Abdominal vagotomy blocks the satiety effect of cholecystokinin in the rat. Science. 1981; 213(4511):1036-7. DOI: 10.1126/science.7268408. View

16.

Park S, Dantzer R, Kelley K, McCusker R . Central administration of insulin-like growth factor-I decreases depressive-like behavior and brain cytokine expression in mice. J Neuroinflammation. 2011; 8:12. PMC: 3045937. DOI: 10.1186/1742-2094-8-12. View

17.

Krueger J, Kubillus S, Shoham S, Davenne D . Enhancement of slow-wave sleep by endotoxin and lipid A. Am J Physiol. 1986; 251(3 Pt 2):R591-7. DOI: 10.1152/ajpregu.1986.251.3.R591. View

18.

Galic M, Riazi K, Pittman Q . Cytokines and brain excitability. Front Neuroendocrinol. 2012; 33(1):116-25. PMC: 3547977. DOI: 10.1016/j.yfrne.2011.12.002. View

19.

Schiffelholz T, Lancel M . Sleep changes induced by lipopolysaccharide in the rat are influenced by age. Am J Physiol Regul Integr Comp Physiol. 2001; 280(2):R398-403. DOI: 10.1152/ajpregu.2001.280.2.R398. View

20.

Khalyfa A, Serpero L, Kheirandish-Gozal L, Sans Capdevila O, Gozal D . TNF-α gene polymorphisms and excessive daytime sleepiness in pediatric obstructive sleep apnea. J Pediatr. 2010; 158(1):77-82. PMC: 3005990. DOI: 10.1016/j.jpeds.2010.07.032. View