Maximal Isometric Contraction Torque Research Articles

Cell transplantation-mediated dystrophin supplementation efficacy in Duchenne muscular dystrophy mouse motor function improvement demonstrated by enhanced skeletal muscle fatigue tolerance

BackgroundDuchenne muscular dystrophy (DMD) is an incurable neuromuscular disease leading to progressive skeletal muscle weakness and fatigue. Cell transplantation in murine models has shown promise in supplementing the lack of the dystrophin protein in DMD muscles. However, the establishment of novel, long-term, relevant methods is needed to assess its efficiency on the DMD motor function. By applying newly developed methods, this study aimed to evaluate the functional and molecular effects of cell therapy-mediated dystrophin supplementation on DMD muscles.MethodsDystrophin was supplemented in the gastrocnemius of a 5-week-old immunodeficient DMD mouse model (Dmd-null/NSG) by intramuscular xenotransplantation of healthy human immortalized myoblasts (Hu5/KD3). A long-term time-course comparative study was conducted between wild-type, untreated DMD, and dystrophin supplemented-DMD mouse muscle functions and histology. A novel GO-ATeam2 transgenic DMD mouse model was also generated to assess in vivo real-time ATP levels in gastrocnemius muscles during repeated contractions.ResultsWe found that 10.6% dystrophin supplementation in DMD muscles was sufficient to prevent low values of gastrocnemius maximal isometric contraction torque (MCT) at rest, while muscle fatigue tolerance, assessed by MCT decline after treadmill running, was fully ameliorated in 21-week-old transplanted mice. None of the dystrophin-supplemented fibers were positive for muscle damage markers after treadmill running, with 85.4% demonstrating the utilization of oxidative metabolism. Furthermore, ATP levels in response to repeated muscle contractions tended to improve, and mitochondrial activity was significantly enhanced in dystrophin supplemented-fibers.ConclusionsCell therapy-mediated dystrophin supplementation efficiently improved DMD muscle functions, as evaluated using newly developed evaluation methods. The enhanced muscle fatigue tolerance in 21-week-old mice was associated with the preferential regeneration of damage-resistant and oxidative fibers, highlighting increased mitochondrial activity, after cell transplantation. These findings significantly contribute to a more in-depth understanding of DMD pathogenesis.

Variation in Limb Support Influences the Time to Task Failure for a Postural Contraction

ABSTRACT The authors compared the time to task failure and muscle activation for a sustained isometric submaximal contraction with the dorsiflexor muscles when the support of the foot varied while supporting an inertial load (position task). Participants performed a supported position task (n = 8) or an unsupported position task (n = 15) while maintaining a constant angle at the ankle with an inertial load equivalent to 20% of maximal isometric contraction torque until task failure. The time to failure for the supported position task (M = 15.4 min, SD = 6.8 min) was longer than for the unsupported position task (M = 10.0 mn, SD = 6.2 min, p = .01). Electromyographic activity of the tibialis anterior differed between tasks (Session × Time, p = .028). Increasing foot support during a position task decreased muscle fatigability and altered activation of the primary agonist indicating the importance of limb support to minimize fatigue during prolonged activation of the dorsiflexor muscles.