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Seven days of muscle re-loading and voluntary wheel running following hindlimb suspension in mice restores running performance, muscle morphology and metrics of fatigue but not muscle strength

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Abstract

In this study, we examined the effects of 2-week hindlimb un-loading in mice followed by re-ambulation with voluntary access to running wheels. The recovery period was terminated at a time point when physical performance—defined by velocity, time, and distance ran per day—of the suspended group matched that of an unsuspended group. Mice were assigned to one of four groups: unsuspended non-exercise (Control), 14 days of hindlimb suspension (HS), 7 days of access to running wheels (E7), or 14 days of HS plus 7 days access to running wheels (HSE7). HS resulted in significant decreases in body and muscle mass, hindlimb strength, soleus force, soleus specific force, fatigue resistance, and fiber cross sectional area (CSA). Seven days of re-ambulation with access to running wheels following HS recovered masses to Control values, increased fiber CSA, increased resistance to fatigue and improved recovery from fatigue in the soleus. HS resulted in a myosin heavy chain (MHC) phenotype shift from slow toward fast-twitch fibers, though running alone did not influence the expression of MHC fibers. Compared to the Control group, HSE7 mice did not recover functional hindlimb strength as assessed through measurements either in vivo or ex vivo. Results from this study demonstrate that 7 days of muscle re-loading with access to wheel-running following HS can stimulate muscle to regain mass and fiber CSA and exhibit improved metrics of fatigue resistance and recovery, yet muscles remain impaired in regard to strength. Understanding this mismatch between muscle morphology and strength may prove of value in designing effective exercise protocols for disuse muscle atrophy rehabilitation.

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Acknowledgments

The authors would like to acknowledge Hans Deiter-Seelig for designing the Labview™ programs necessary for HEFT and electrophysiology data collection. We would also like to express our sincere thanks to the Leinwand Lab in the Department of Molecular, Cellular, and Developmental Biology at the University of Colorado for providing the antibodies used to stain for MHC-IIa, MHC-IIX, and MHC-IIb expressing fibers. Finally, we acknowledge and thank Brooke Harrison for his guidance and technical support of the immunohistochemical methods and analysis. Fundings by BioServe Space Technologies and NASA Cooperative Agreement NCC8-242.

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Authors and Affiliations

  1. Aerospace Engineering Sciences, BioServe Space Technologies, University of Colorado, Boulder, CO, USA

    Andrea M. Hanson, Louis S. Stodieck, Cara M. A. Cannon & Steven J. Simske

  2. Mechanical Engineering, University of Colorado, UCB 427, Boulder, CO, 80309, USA

    Virginia L. Ferguson

  3. Hewlett-Packard Labs, Palo Alto, CA, USA

    Steven J. Simske

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  1. Andrea M. Hanson
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  2. Louis S. Stodieck
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  3. Cara M. A. Cannon
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  4. Steven J. Simske
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  5. Virginia L. Ferguson
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Correspondence to Virginia L. Ferguson.

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Hanson, A.M., Stodieck, L.S., Cannon, C.M.A. et al. Seven days of muscle re-loading and voluntary wheel running following hindlimb suspension in mice restores running performance, muscle morphology and metrics of fatigue but not muscle strength. J Muscle Res Cell Motil 31, 141–153 (2010). https://doi.org/10.1007/s10974-010-9218-5

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