Skeletal muscle atrophy in the Veteran population is extremely common and may arise due to poor nutrition, denervation, head injury, limb trauma, cancer, ageing, and disuse. Atrophy results from mechanical unloading of muscle over a prolonged period, resulting in reduced muscle mass, area, and strength (without a reduction of myofibers) and can be disabling. For almost a century it has been known that transient exposure to glucocorticoids (GC) enhances physical performance and increases endurance. Paradoxically, despite these performance enhancing benefits, GC are not routinely prescribed for non-inflammatory diseases since standard daily GC dosing regimens cause marked muscle atrophy. In this SPiRE grant, we will test the hypothesis that once-weekly steroid administration in a muscle atrophy model improves muscle function and growth. Muscle atrophy will be induced in mice by cast immobilization, as prolonged casting is a common event that induces atrophy in Veterans and does not disrupt neurovascular structures. The experimental design is a two-way ANOVA model with seven groups of mice, randomized with equal numbers of male and female mice (n=6 mice total per group). Mice will be dosed with 0.1mg/kg or 1mg/kg of prednisone steroid during casting, post casting (recovery) or both during casting and during recovery. PBS ?dosing? will be used as a control. Muscle force generation, gene expression, size, endurance capacity and muscle mass measured after each of these treatments. The data generated from this SPiRE grant will enable design of a human study that refines these treatments in the Veteran population.
Skeletal muscle atrophy is a common problem among Veterans. Atrophy results from chronic disease, cachexia, denervation, trauma and disuse. Muscle atrophy is common to a number of Veterans who experience stroke, orthopaedic trauma, neurodegenerative diseases and nearly every Veteran who experiences prolonged bedrest after injury. Enhancing muscle growth and/or preventing muscle loss would dramatically improve the health and function of our Veterans and is even the goal of a multibillion dollar pharmaceutical industry. Accelerated muscle growth or inhibition of muscle loss could be advantageous in each of these conditions to promote more rapid healing and recovery from injury. To achieve these goals, we will define the optimal dosing and timing of GC administration to prevent atrophy onset and improve the recovery from atrophy. The experiments in this SPiRE grant will provide the preliminary data required to design a more extensive grant to study this phenomenon in humans.
