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Study may explain exercise-induced fatigue in muscular dystrophies
Date:10/26/2008

ch associate in molecular physiology and biophysics, showed that mice with misplaced or missing nNOS exhibited prolonged fatigue after mild exercise.

"The mice without nNOS have normal muscles and can exercise quite well, but after just mild exercise, we found that they had the intense fatigue response," Kobayashi said.

Blood vessel imaging of these mice showed post-exercise constriction of the blood vessels supplying muscle. Blocking nNOS activity in normal mice also produced post-exercise fatigue and narrowed blood vessels to the muscles.

The team also found that although gene therapy could restore the structure and function of an important component of muscle membranes in mice with muscular dystrophy, this treatment did not alleviate the post-exercise fatigue. Further analysis showed that although the muscle membrane complex was intact, nNOS was still not correctly localized to the membrane, and blood vessels supplying skeletal muscle were abnormally constricted after mild exercise.

"The signaling pathway probably maintains blood flow into the muscle during exercise and keeps the blood flow going after exercise. But when nNOS is missing or mislocalized, this pathway breaks down," Campbell explained. "The mice with mislocalized nNOS are able to exercise, but after exercise that reduced blood flow to the recovering muscles produces the fatigue."

To determine if nNOS was affected in humans with muscular dystrophy, Steven Moore, M.D., Ph.D., UI professor of pathology and study co-author, examined muscle biopsies from 425 patients with many different forms of muscular dystrophy. He found that nNOS was missing or reduced in most cases, suggesting a common mechanism of fatigue.

"Our findings could lead to a better understanding of fatigue under other physiological conditions in which muscle nNOS expression, localization, or activity is affected," Kobayashi added.

The enzyme nNOS makes a signaling molecule
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Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-335-9917
University of Iowa
Source:Eurekalert

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