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.
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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ABSTRACT: Skeletal muscle structure and function are markedly affected by chronic disuse. With unloading, muscle mass is lost at rate of about 0.4 %/day but little is known about the recovery of muscle mass and strength following disuse. Here we report an extensive data set describing in detail skeletal muscle adaptations in structure and function in response to both disuse and retraining. Eight young men (23 ± 2.2 years) underwent 3 weeks of unilateral lower limb suspension (ULLS) followed by a 3-week resistance training recovery program. Knee extensor isometric torque, voluntary activation, quadriceps femoris (QF) muscle volume (QFvol), fascicle length (Lf) and pennation angle (θ), physiological cross-sectional area (PCSA) of all four heads of the QF muscle, were measured before, after ULLS, and post-ULLS-resistance training. Needle biopsies were taken from the vastus lateralis muscle of a subgroup (n = 6) of the same subjects and cross sectional area of individual muscle s and myosin content of muscle samples were determined. Following 3 weeks of ULLS, isometric torque decreased by 26 %, PCSA by 3 %, QFvol by 10 %. Lf and θ of all four heads of QF significantly decreased (p ≤ 0.05). Following the 3-week retraining period, isometric torque, PCSA, QFvol, Lf and θ of all four heads of QF were all fully restored to pre ULLS values. CSA of individual muscle fibres and myosin content of muscle samples decreased by 26 and 35 % respectively (post-ULLS) and recovered to almost pre-ULLS values following retraining. There were no significant changes in voluntary activation of the quadriceps muscles in response to either ULLS or subsequent retraining. These results indicate that: (1) the loss of muscle force with 3-week unloading in humans is mostly explained by muscle atrophy and by a decrease in myosin content and, (2) all the neuromuscular changes induced by this model of disuse can be fully restored after a resistance training intervention of equal duration.Biogerontology 05/2013; · 3.19 Impact Factor
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ABSTRACT: Hindlimb unloading-induced muscle atrophy is often assessed after a homeostatic state is established, thus overlooking the early adaptations that are critical to developing this pattern of atrophy. Muscle function and physiology were characterized at 0, 1, 3, 7, and 14 days of hindlimb suspension (HS). Reductions in muscle mass were maximal by Day 14 of HS. Functional strength and isolated muscle strength were reduced. MyHC-I and -IIa expressing fibers were reduced in size by Day 7 in the soleus and by Day 14 in the gastrocnemius (MyHC-I fibers only). Atrogin-1 and MuRF1 expression was increased by Day 1 in both the calf and tibialis anterior while IGF-1 expression was significantly reduced on Day 3. Phosphorylation of Akt was reduced on Day 14. Insight into these early changes in response to HS improves understanding of the molecular and functional changes that lead to muscle atrophy. Muscle Nerve, 2013.Muscle & Nerve 12/2012; · 2.31 Impact Factor
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ABSTRACT: Matrix metalloproteinases (MMPs) play a major role in the degradation of the extracellular matrix (ECM) of skeletal muscle, and the inducible gelatinase MMP-9 in particular appears to be critical for the remodeling of muscle ECM during growth and repair. Here we determined the effects of MMP-9 gene inactivation on fiber type and size in the tibialis anterior (TA), gastrocnemius (GAST), and soleus (SOL) muscles in female mice. In the TA, the cross-sectional area (CSA) of the myosin heavy chain (MyHC) IIb-expressing fibers was significantly smaller in MMP-9 null mice while in the GAST, CSA of all three fast fiber types was decreased. In the SOL, MyHC type I-expressing fibers were significantly smaller in the MMP-9 null mice. The percentage of MyHC type IIb-expressing fibers was significantly increased in the TA and GAST of MMP-9 null mice, while the percentage of MyHC IId-expressing fibers significantly decreased in the GAST of MMP-9 null mice. Fiber percentages in the SOL were not significantly different between the two lines. Despite these changes in fiber size and type, in vivo hindlimb force production was not changed in MMP-9 null mice. Meanwhile, neither expression of the constitutive gelatinase MMP-2 nor immunohistochemical staining for type IV collagen was significantly altered by MMP-9 inactivation in any muscles examined. The present study demonstrates that MMP-9 inactivation results in changes in fiber size and type in adult mouse hindlimb muscles that may depend on indirect mechanisms involving reduced bone growth or nerve changes in response to MMP-9 inactivation.Cells Tissues Organs 03/2011; 194(6):510-20. · 1.96 Impact Factor