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.
- SourceAvailable from: Jorge Lira Ruas[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.Cell 12/2012; 151(6):1319-31. DOI:10.1016/j.cell.2012.10.050 · 33.12 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 09/2013; 48(3). DOI:10.1002/mus.23753 · 2.31 Impact Factor
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ABSTRACT: Background: The change in the cross-sectional area of a repaired muscle, measured with use of magnetic resonance imaging (MRI), could be an indicator of recovery of muscle function. The aims of this study were to evaluate the change in the area of the supraspinatus muscle between the immediately postoperative and one-year postoperative MRIs and to identify factors associated with the change. Methods: Eighty-eight patients with a full-thickness rotator cuff tear were included. MRI was performed three days and one year after surgery. Patients were classified into two groups according to whether the area of the supraspinatus increased or decreased between these two time points. Outcomes including pain, shoulder motion, strength, and commonly used clinical scores were assessed preoperatively and at three, six, and twelve months after surgery. Changes in the rotator cuff muscles and retear of the repaired tendon were also evaluated. Results: The area of the supraspinatus muscle increased in twenty-nine (33%) of the patients and decreased in fifty-nine (67%). The change in area was 36.75 +/- 27.94 mm(2) in the group in which it increased and -94.25 +/- 70.38 mm(2) in the group in which it decreased (p < 0.001). Multiple regression analysis indicated that a lower preoperative Simple Shoulder Test (SST) score, better gross visual grade of the tendon at surgery, and greater strength of the supraspinatus at six months postoperatively were associated with an increase in the area. No retear or Sugaya grade of 3 was found in any patient in whom the area increased, whereas 34% of the patients in whom the area decreased had a retear (p < 0.001). Conclusions: This study showed that the cross-sectional area of the supraspinatus muscle could either increase or decrease during the first year after rotator cuff repair and that robust healing (indicated by a Sugaya grade of 1 or 2) and good tendon quality at surgery were important factors associated with an increase in the area.The Journal of Bone and Joint Surgery 10/2013; 95(19):1785-1791. DOI:10.2106/JBJS.L.00938 · 4.31 Impact Factor