title: Effects of voluntary wheel running on LPS-induced sickness behavior in aged mice.
abstract: Peripheral stimulation of the innate immune system with LPS causes exaggerated neuroinflammation and prolonged sickness behavior in aged mice. Regular moderate intensity exercise has been shown to exert anti-inflammatory effects that may protect against inappropriate neuroinflammation and sickness in aged mice. The purpose of this study was to test the hypothesis that voluntary wheel running would attenuate LPS-induced sickness behavior and proinflammatory cytokine gene expression in ~22-month-old C57BL/6J mice. Mice were housed with a running wheel (VWR), locked-wheel (Locked), or no wheel (Standard) for 10 weeks, after which they were intraperitoneally injected with LPS across a range of doses (0.02, 0.08, 0.16, 0.33 mg/kg). VWR mice ran on average 3.5 km/day and lost significantly more body weight and body fat, and increased their forced exercise tolerance compared to Locked and Shoebox mice. VWR had no effect on LPS-induced anorexia, adipsia, weight-loss, or reductions in locomotor activity at any LPS dose when compared to Locked and Shoebox groups. LPS induced sickness behavior in a dose-dependent fashion (0.33>0.02 mg/kg). Twenty-four hours post-injection (0.33 mg/kg LPS or Saline) we found a LPS-induced upregulation of whole brain TNFα, IL-1β, and IL-10 mRNA, and increased IL-1β and IL-6 in the spleen and liver; these effects were not attenuated by VWR. We conclude that VWR does not reduce LPS-induced exaggerated or prolonged sickness behavior in aged animals, or 24h post-injection (0.33 mg/kg LPS or Saline) brain and peripheral proinflammatory cytokine gene expression. The necessity of the sickness response is critical for survival and may outweigh the subtle benefits of exercise training in aged animals.
authors.affiliation: Departments of Kinesiology and Community Health, University of Illinois @Urbana-Champaign, Urbana IL, United States; Integrated Immunology and Behavior Program, University of Illinois @Urbana-Champaign, Urbana IL, United States.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Martin
authors.affiliation: Departments of Kinesiology and Community Health, University of Illinois @Urbana-Champaign, Urbana IL, United States; Integrated Immunology and Behavior Program, University of Illinois @Urbana-Champaign, Urbana IL, United States.
authors.forename: Brandt D
authors.initials: BD
authors.lastname: Pence
authors.affiliation: Departments of Kinesiology and Community Health, University of Illinois @Urbana-Champaign, Urbana IL, United States.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Greene
authors.affiliation: Departments of Kinesiology and Community Health, University of Illinois @Urbana-Champaign, Urbana IL, United States.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Johnson
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Robert
authors.initials: R
authors.lastname: Dantzer
authors.affiliation: Integrated Immunology and Behavior Program, University of Illinois @Urbana-Champaign, Urbana IL, United States; Department of Animal Sciences, University of Illinois @Urbana-Champaign, Urbana, IL, United States.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Kelley
authors.affiliation: Departments of Kinesiology and Community Health, University of Illinois @Urbana-Champaign, Urbana IL, United States; Integrated Immunology and Behavior Program, University of Illinois @Urbana-Champaign, Urbana IL, United States. Electronic address: woods1@illinois.edu.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Woods
mesh_terms: D000375:Aging / Q000523:psychology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005221:Fatigue / Q000523:psychology; D015870:Gene Expression / Q000187:drug effects; D055809:Illness Behavior / Q000187:drug effects*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D012420:Running / Q000523:psychology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D012313:RNA