Voluntary wheel running does not affect lipopolysaccharide-induced depressive-like behavior in young adult and aged mice

Neuroimmunomodulation. 2014;21(1):52-63. doi: 10.1159/000356144. Epub 2013 Nov 20.

Abstract

Objective(s): Peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes prolonged depressive-like behavior in aged mice that is dependent on indoleamine 2,3 dioxygenase (IDO) activation. Regular moderate-intensity exercise training has been shown to exert neuroprotective effects that might reduce depressive-like behavior in aged mice. The purpose of this study was to test the hypothesis that voluntary wheel running (VWR) would attenuate LPS-induced depressive-like behavior and brain IDO gene expression in 4- and 22-month-old C57BL/6J mice.

Methods: Mice were housed with a running wheel (VWR) or no wheel (standard) for 30 (young adult mice) or 70 days (aged mice), after which they were intraperitoneally injected with LPS (young adult mice: 0.83 mg/kg; aged mice: 0.33 mg/kg).

Results: Young adult VWR mice ran on average 6.9 km/day, while aged VWR mice ran on average 3.4 km/day. Both young adult and aged VWR mice increased their forced exercise tolerance compared to their respective standard control groups. VWR had no effect on LPS-induced anorexia, weight loss, increased immobility in the tail suspension test and decreased sucrose preference in either young adult or aged mice. Four (young adult mice) and 24 h (aged mice) after injection of LPS, mRNA transcripts for TNF-α, IL-1β, IL-6, and IDO were upregulated in the whole brain independently of VWR.

Conclusion: Prolonged physical exercise has no effect on the neuroinflammatory response to LPS and its behavioral consequences in young adult and aged mice.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / physiology*
  • Animals
  • Body Weight / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Depression / chemically induced*
  • Depression / rehabilitation*
  • Disease Models, Animal
  • Exercise Test
  • Exercise Therapy / methods*
  • Fatigue / chemically induced
  • Food Preferences / drug effects
  • Gene Expression Regulation / drug effects
  • Hindlimb Suspension
  • Lipopolysaccharides / toxicity*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Running*
  • Sickness Impact Profile

Substances

  • Cytokines
  • Lipopolysaccharides