Effects of voluntary wheel running and forced treadmill running on inflammation induced behavioral abnormalities in young and old mice

Peripheral infection stimulates the innate immune system to produce pro-inflammatory cytokines, such as tumor-necrosis-factor-α, interleukin-1β, and interleukin-6, which signal through various communication pathways to induce a ‘mirror image’ of cytokine expression within the brain. Centrally, these pro-inflammatory cytokines act directly or indirectly on neurons and supporting cells to alter autonomic nervous system output, endocrine system output, and behavior to regulate the body’s response to infection. One host factor affecting the behavioral response to infection is aging. Due to microglia priming and exacerbated neuroinflammation, aged individuals exhibit prolonged sickness behavior and depressive-like behavior following activation of the immune system. Regular moderate intensity exercise has been show to exert neuroprotective effects that may protect against inappropriate neuroinflammation and behavioral disturbances in aged subjects. The purpose of these studies was to investigate the effects of voluntary wheel running and forced treadmill running on lipopolysaccharide (LPS) and Bacillus Calmette-Guérin (BCG) induced sickness behavior (food intake, fluid intake, body weight, locomotor activity), depressive-like behavior (tail suspension test, sucrose preference), and activation of brain cytokine signaling pathways in young adult and aged mice. We hypothesized voluntary wheel running prior to LPS administration would induce anti-inflammatory effects and attenuate LPS-induced sickness behavior and depressive-like behavior. In contrast, we hypothesized forced treadmill exercise following BCG inoculation would exacerbate BCG-induced sickness behavior. Voluntary wheel running induced expected adaptations including body weight loss, fat loss, and improved forced exercise tolerance. However, voluntary wheel running did not protect against LPS-induced sickness behavior, depressive-like behavior, or whole brain proinflammatory cytokine and indoleamine 2,3-dioxygenase gene expression in young adult and aged mice. Forced treadmill running following BCG inoculation caused protracted recovery from infection as evidenced by prolonged body weight loss, reduced voluntary wheel running, and a tendency for reduced sucrose preference. Thus, while exercise has been shown to be neuroprotective and anti-inflammatory, we did not observe that in our model. Possible explanations for the deviance include: inflammatory model, timing of exercise in relation to immune challenge, and brain regions responsible for behavioral response. Future research is necessary to understand the effects of exercise on microglia priming and how this affects behavioral outcomes. Finally, translational research should investigate the effects of regular exercise training prior to, and after infection, on perceived sickness behaviors and depression progression in aged adults.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Kinesiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2013

Author dc:creator

• Martin, Stephen

Contributors dc:contributor

• Woods, Jeffrey A.
• Wilund, Kenneth R.
• Boppart, Marni M.
• Dantzer, Robert

• Aging
• Sickness Behavior
• Depression
• Depressive-like Behavior
• Exercise
• Voluntary Wheel Running
• Inflammation

Statement dc:rights

• Copyright 2013 Stephen Martin

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/45336

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/45336