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
Aerospace Engineering Sciences, BioServe Space Technologies, University of Colorado, Boulder, CO, USA. Journal of Muscle Research and Cell Motility
(Impact Factor: 2.09).
08/2010; 31(2):141-53. DOI: 10.1007/s10974-010-9218-5
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.
Available from: Jorge Lira Ruas
- "HS was performed as described previously (Hanson et al., 2010). All protocols were approved by the University of Colorado Institutional Animal Care and Use Committee. "
[Show abstract] [Hide abstract]
ABSTRACT: PGC-1α is a transcriptional coactivator induced by exercise that gives muscle many of the best known adaptations to endurance-type exercise but has no effects on muscle strength or hypertrophy. We have identified a form of PGC-1α (PGC-1α4) that results from alternative promoter usage and splicing of the primary transcript. PGC-1α4 is highly expressed in exercised muscle but does not regulate most known PGC-1α targets such as the mitochondrial OXPHOS genes. Rather, it specifically induces IGF1 and represses myostatin, and expression of PGC-1α4 in vitro and in vivo induces robust skeletal muscle hypertrophy. Importantly, mice with skeletal muscle-specific transgenic expression of PGC-1α4 show increased muscle mass and strength and dramatic resistance to the muscle wasting of cancer cachexia. Expression of PGC-1α4 is preferentially induced in mouse and human muscle during resistance exercise. These studies identify a PGC-1α protein that regulates and coordinates factors involved in skeletal muscle hypertrophy.
Available from: Ryan S Mehan
[Show abstract] [Hide abstract]
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.
Available from: Yanlei Hao
[Show abstract] [Hide abstract]
ABSTRACT: βHydroxy-β-methylbutyrate (HMB) is a leucine metabolite shown to reduce protein catabolism in disease states and promote skeletal muscle hypertrophy in response to loading exercise. In this study, we evaluated the efficacy of HMB to reduce muscle wasting and promote muscle recovery following disuse in aged animals. Fisher 344×Brown Norway rats, 34 mo of age, were randomly assigned to receive either Ca-HMB (340 mg/kg body wt) or the water vehicle by gavage (n = 32/group). The animals received either 14 days of hindlimb suspension (HS, n = 8/diet group) or 14 days of unloading followed by 14 days of reloading (R; n = 8/diet group). Nonsuspended control animals were compared with suspended animals after 14 days of HS (n = 8) or after R (n = 8). HMB treatment prevented the decline in maximal in vivo isometric force output after 2 wk of recovery from hindlimb unloading. The HMB-treated animals had significantly greater plantaris and soleus fiber cross-sectional area compared with the vehicle-treated animals. HMB decreased the amount of TUNEL-positive nuclei in reloaded plantaris muscles (5.1% vs. 1.6%, P<0.05) and soleus muscles (3.9% vs. 1.8%, P<0.05). Although HMB did not significantly alter Bcl-2 protein abundance compared with vehicle treatment, HMB decreased Bax protein abundance following R, by 40% and 14% (P<0.05) in plantaris and soleus muscles, respectively. Cleaved caspase-3 was reduced by 12% and 9% (P<0.05) in HMB-treated reloaded plantaris and soleus muscles, compared with vehicle-treated animals. HMB reduced cleaved caspase-9 by 14% and 30% (P<0.05) in reloaded plantaris and soleus muscles, respectively, compared with vehicle-treated animals. Although, HMB was unable to prevent unloading-induced atrophy, it attenuated the decrease in fiber area in fast and slow muscles after HS and R. HMB's ability to protect against muscle loss may be due in part to putative inhibition of myonuclear apoptosis via regulation of mitochondrial-associated caspase signaling.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.