Effects of Treadmill Exercise and High-Fat Feeding on Muscle Degeneration in Mdx Mice at the time of Weaning

Abstract

1. Dystrophin-deficient hindlimb muscles of mdx mice undergo necrosis at the time of weaning when the motor activity of the mice greatly increases and muscle energy metabolism becomes more dependent on insulin and carbohydrates. 2. We have attempted to determine if the onset of myofibre necrosis in mdx mice at the time of weaning is related to the development of motor activity and/or the change in diet. 3. Fourteen-day-old mdx mice were divided into two groups after weaning. One group was trained to run on a treadmill and the other group was kept on a high-fat diet. Muscle necrosis was assessed histologically in the soleus and extensor digitorum longus muscles of mice in both experiments. 4. Keeping mice on a high-fat milk diet from the time of weaning up to 42 days of age did not influence the occurrence of necrosis in the soleus and extensor digitorum longus muscles of the mdx pups. In contrast, treadmill exercise greatly increased necrosis in both muscles. 5. We conclude that an increase in motor activity exacerbates the degeneration of hindlimb muscles of mdx mice at the time of weaning.

Evidence ofmdx mouse skeletal muscle fragility in vivo by eccentric running exercise

“…4,10,38 This cycle is supposed to be due to increased exploratory behavior and locomotor activity of the pups and may be accentuated by running exercise. 30 The adult mdx mice and mdx skeletal muscles are generally bigger and heavier than control mice; however, mdx muscle fibers are weaker when the strength is reported to their cross-sectional area. The skeletal muscles do not show extensive fibrosis, except the diaphragm, which is one of the most constantly solicited skeletal muscles.…”

“…Some animals were also submitted to acute or chronic physical exercise. 1,6,17,27,30,33,40,45 Eccentric exercise protocols were developed ex vivo or in vivo in different muscle groups in rat, mouse, and human. The principle of eccentric exercise is based on the contraction of a lengthened muscle fiber.…”

Decreased Mitochondrial Oxygen Consumption and Antioxidant Enzyme Activities in Skeletal Muscle of Dystrophic Mice after Low-Intensity Exercise

“…At 4 weeks (young) and 16 weeks (adult) of age, control and mdx mice were randomly assigned to the four groups (n = 10 per group): control sedentary, control exercised, mdx sedentary and mdx exercised. The age of 4 weeks was chosen to initiate the exercise training, because at this age mdx mice have not yet gone through the accelerated degenerative necrotic stage of the disease [10], although hindlimb muscle necrosis is known to start at 3-4 weeks of age [31,39]. In contrast, adult mdx mice go through a phase of regeneration and thus do not suffer long-term muscle weakness as indicated by functional and histochemical signs [3].…”

“…Although eccentric exercise is known to damage muscle fibres [4], both harmful [31,42] and beneficial [8,13,18] effects on mdx skeletal muscles are reported.…”

Dystrophin Degradation in Skeletal Muscles with Lipid Enrichment in Cattle

“…In case of dystrophin deficiency, which is well-established in mdx mice, hind limb muscles of mdx mice undergo necrosis at the time of weaning when the motor activity of the mice greatly increases and muscle energy metabolism becomes more dependent on insulin and carbohydrates [19,29]. Null mutation of any one of several members of the dystrophin protein complex can cause progressive, and possibly fatal, muscle wasting.…”