Abstract
Voluntary wheel running can potentially be used to exacerbate the disease phenotype in dystrophin-deficient mdx mice. While it has been established that voluntary wheel running is highly variable between individuals, the key parameters of wheel running that impact the most on muscle pathology have not been examined in detail. We conducted a 2-week test of voluntary wheel running by mdx mice and the impact of wheel running on disease pathology. There was significant individual variation in the average daily distance (ranging from 0.003 ± 0.005 km to 4.48 ± 0.96 km), culminating in a wide range (0.040 km to 67.24 km) of total cumulative distances run by individuals. There was also variation in the number and length of run/rest cycles per night, and the average running rate. Correlation analyses demonstrated that in the quadriceps muscle, a low number of high distance run/rest cycles was the most consistent indicator for increased tissue damage. The amount of rest time between running bouts was a key factor associated with gastrocnemius damage. These data emphasize the need for detailed analysis of individual running performance, consideration of the length of wheel exposure time, and the selection of appropriate muscle groups for analysis, when applying the use of voluntary wheel running to disease exacerbation and/or pre-clinical testing of the efficacy of therapeutic agents in the mdx mouse.
Highlights
Duchenne muscular dystrophy (DMD) is a prevalent neuromuscular disease resulting from a mutation affecting the dystrophin gene, and resulting in widespread deficiency of the muscle membrane protein, dystrophin [1] [2]
The results of this study clearly demonstrate extensive individual variation in voluntary wheel running in adult mdx mice
As the number of running bouts equates with the number of rest breaks, it can be extrapolated that a low number of rest breaks correlates with increased muscle damage
Summary
Duchenne muscular dystrophy (DMD) is a prevalent neuromuscular disease resulting from a mutation affecting the dystrophin gene, and resulting in widespread deficiency of the muscle membrane protein, dystrophin [1] [2]. This causes a loss of membrane integrity, and muscle susceptibility to damage and degeneration. It has been suggested that the mdx dystrophic phenotype can be exacerbated to more closely resemble human DMD pathology by exposing animals to an exercise regime. Exercise regimes have been utilized to exacerbate the dystrophic phenotype and allow investigation of key characteristics and mechanisms of muscle weakness and degeneration [5] , and to increase the rigor of pre-clinical testing of therapeutic agents [6] [7] [8] [9] [10]
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