Date of Graduation
School of Medicine
Physiology, Pharmacology & Neuroscience
Stephen E Alway
Randall W Bryner
Junaith S Mohamed
Janet C Tou
The reloading of atrophied muscles from weightlessness or disuse results in injury and prolonged recovery. Satellite cells, or muscle stem cells, have a key role in facilitating injury-induced muscle repair but have not been shown to be required in muscle remodeling following atrophy. However, it has been less clear if low-impact exercise, such as voluntary wheel running, could provide a sufficient stimulus to enhance muscle recovery from atrophy through satellite cell activation. This study aimed to determine if voluntary wheel running improved recovery from muscle disuse following hindlimb suspension unloading (HSU), and if the recovery was associated with exercise-induced satellite cell activity. Young adult male and female C57BL/6 background mice (n=6/group) were subjected to either 14 days of normal weight bearing, 14 days of HSU, 14 days of HSU + 14 days of re-ambulation, 14 days of voluntary wheel running, or 14 days of HSU + 14 days of voluntary wheel running. Mice were given 5-bromo-2'-deoxyuridine (BrdU) in their drinking water during the final 14 days of the experiment to measure satellite cell proliferation in gastrocnemius muscle fibers. HSU significantly reduced in vivo maximal force and decreased the rate of fatigue in the plantarflexor muscles. Voluntary wheel running during reloading after HSU significantly improved resistance to fatigue, which was associated with significant increases in both muscle fiber cross sectional area (CSA) and an increased percentage of oxidative type IIA muscle fibers in the gastrocnemius muscle as compared to the mice recovering without exercise. BrdU positive nuclei that had proliferated and were located inside the muscle sarcolemma were identified by immunohistochemical labeling and quantified in tissue cross sections. Following HSU, wheel running mice had a significantly greater percentage of BrdU positive nuclei that were inside gastrocnemius muscle fibers. Western blot analysis showed HSU mice with wheel running had a higher MyoD to Pax7 ratio as compared to mice that did not exercise after HSU. Mice in the wheel running group had significantly improved fatigue resistance, a significantly increased oxidative fiber phenotype, and significantly increased fiber CSA as compared to non-exercised animals after HSU. These results indicate that voluntary wheel running increased satellite cell activity during the recovery phase following HSU and this was associated with improved recovery from muscle disuse. While satellite cells did not exhibit increased activity in passive recovery (non-wheel running), manipulating their activation through low-impact exercise appeared to enhance morphological recovery and improve muscle function.
Brooks, Matthew J., "Voluntary Wheel Running Improves Recovery from Muscle Disuse in Mice" (2016). Graduate Theses, Dissertations, and Problem Reports. 5263.