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Four related studies from the laboratory of Assistant Professor Monika Fleshner of the University of Colorado at Boulder suggest physiological responses to stress from the brain, hormonal system and immune system are moderated by regular exercise.

Fleshner, of the kinesiology and applied physiology department, said the research team is seeking a "top-down" explanation of how and why regular exercise affects stress. Doctors know that people who exercise regularly are less likely to get sick after stressful situations than those who donÂ’t exercise, and that exposure to mental or physical stress increases a personÂ’s susceptibility to illness or disease, she said.

Reactions to stress begin in the brain, Fleshner said. In one study led by ¶¶Òõ¶ÌÊÓƵ-Boulder doctoral student Justin Hinde, rats that chose to run on a wheel for four weeks prior to experiencing 90 minutes of moderate stress were shown to have changes in stress-reactive brain circuits. This was determined by measuring the amount of Fos protein produced in stress-reactive brain areas.

Rats that had been running on a wheel before stress had lower amounts of Fos protein in the pre-frontal cortex, septum and amygdala of the brain. Fos protein is a neural activation marker produced by activation of the gene known as c-fos. "What these reductions mean to the animals remains unknown, although it could result in less of a sympathetic nervous system response to stress," Fleshner said.

"It appears the stress circuit begins in the brain at the pre-frontal cortex, and that after stress, wheel-running rats have less neural activity in this area than sedentary rats," she said. The results of the ¶¶Òõ¶ÌÊÓƵ-Boulder studies will be presented at the Annual Meeting of the Society for Neuroscience Oct. 23 to Oct. 28 in Miami.

A second study led by ¶¶Òõ¶ÌÊÓƵ-Boulder doctoral student Taro Smith examined neuro-hormonal responses to stress. The results indicated regularly exercising rats release less norepinephrine -- an adrenaline-like hormone -- than sedentary rats when both groups were under stress. Smith likened the effects of norepinephrine to the alarm a person might feel after inadvertently running a red light.

The third study, spearheaded by Fleshner, was designed to look at differences in bacterial inflammation between groups of exercising rats and sedentary rats, both of which also were stressed. Researchers know that stress in sedentary rats can alter the development and healing time of inflammation caused by bacterial infections.

The results indicated that stress in sedentary rats infected with E. coli bacteria reduced the amount of inflammation initially caused by the bacteria, said Fleshner. But stressed rats that had been regularly running on a wheel and then infected showed an increase in bacteria-attacking white blood cells migrating to the infection site, causing the healing time to speed up by three to four days compared to the sedentary rat group.

"An analogy might be a sedentary person on a challenging mountain hike cutting his hand on a sharp rock and introducing bacteria into the wound," said Fleshner. "That person’s body probably would not be able to ‘clean up’ the infection site as quickly or efficiently as an experienced, active mountain climber’s body."

The fourth study headed by ¶¶Òõ¶ÌÊÓƵ doctoral student Albert Moraska was designed to understand how physical activity mitigates immunological responses to stress at the cellular level. The researchers measured white blood cellular division, cytokine release (proteins released by lymphocytes during immune responses), and elevations in heat shock proteins (cellular proteins that increase in cells during times of stress) in both exercising and sedentary rat groups.

They concluded that the rats that ran on wheels before stress were significantly less affected by the negative effect of stress, including the suppression of cell division, decreases in cytokines and increases in the production of stress proteins. In fact, the physically active stressed rats had elevated levels of interleukin-2 and interferon-g, proteins essential for fighting disease.

"Our goal is to understand how regular, moderate, physical activity alters the stress response by examining the entire system, from the brain to the individual cells," said Fleshner. "We think we have the pieces mapped out, but we still need to show how one leads to another."

Other researchers involved in the four studies included ¶¶Òõ¶ÌÊÓƵ kinesiology and applied physiology Professors Roger Enoka and Robert Mazzeo, Professor Earl Noble of the University of Western Ontario, ¶¶Òõ¶ÌÊÓƵ research associates Sophi De Serrez, John Semmler, and Ronald Gaykema, ¶¶Òõ¶ÌÊÓƵ graduate students Jennifer Kintzel, Ted Leem, Terrence Deak, Bristol Sorenson, and undergraduates Karianne Higgins and Mary Nickerson.