Proceedings of The Physiological Society

University College Dublin (2009) Proc Physiol Soc 15, PC24

Poster Communications

Exercise for a precocious detection of impairment in mdx mice model

L. Mille-Hamard1, E. Henry1, V. L. Billat1

1. Universite Evry-Val d'Essonne, UBIAE INSERM U902, Evry, France.

  • Figure 1 : Change in performance parameters (percentage) of control (n = 7) and mdx (n = 6) mice at 9 months compared with 5 months. VO2max: maximal oxygen consumption. Vpeak: maximal velocity reached. vVO2max: velocity associated with VO2max. CS: critical speed.

The mdx mouse with essential dystrophin deficiency is an established animal model of Duchenne’s muscular dystrophy (DMD) in human. However, hindlimb muscle of mdx mice does not exhibit severe and progressive muscle weakness before 15 month , which is late compared to DMD patients, excepted for the diaphragm that is severely affected earlier by the disease (Dupont-Versteegden, 1996). More over respiratory function seems to be decreased at muscle level, mdx muscle mitochondria had only 60% of maximal respiration activities of control mice skeletal muscle mitochondria (Kuznetsov et al., 1998). However how the diaphragm and these less efficient mitochondrion affect the whole body performance (running velocity and maximal oxygen consumption) in young and older mice was not established. As mice are animals with mostly anaerobic displacements and mdx mice are not severely impaired before 15 months, we hypothesized that running performance should not be greatly affected conversly to maximal oxygen consumption in mice between 5 and 9 months. Six mdx mice of 5 months and 6 mdx mice of 9 months of age were tested on a treadmill inserted in a metabolic chamber (Columbus Instrument). Exercise protocols were performed to determine maximal (Vpeak) and critical velocity (CS) as well as VO2max (Billat et al. 2005, Ferreira et al., 2007).and the corresponding velocity (vVO2max) Results are compared with 7 control mice aged 5 and 9 months. Results showed that at 5 months VO2max of mdx mice was not different from control (49.38 ± 5.48 vs 48.14 ± 3.24, p = 0.639). However mdx mice performed higher Vpeak (26.20 ± 2.26 vs 19.86 ± 2.27, p = 0.001)and vVO2max was higher (25.5 ± 2.26 vs 15.57 ± 3.21, p < 0.001). Surprisingly VO2max did not deacreased between 5 and 9 months old mdx mice. Even more the decreased of other parameters of performance between 5 and 9 months (vVO2max, CS, Vpeak) were more severe in mdx than in control mice (Figure 1). These results indicate that all parameters of performance in mdx mice were affected differently and physiological speeds decreased before the hindlimb muscle impairment. The metabolism of running mdx mice differed marquedly from control and this can explain beneficial effects of exercice previously demonstrated (Kaczor et al., 2007). Exercise allowed to underline defficiency precociously (9 months) compared with other in vivo parameters used in the litterature (around 15 months). Further analyses are in progress to determine the respective part of the diaphragm and skeletal muscle energetics impairment responsible for this severe decrease of performance in mdx mice. Thus exercise can be a usefull tool for pathological models, included in the mdx model.

Where applicable, experiments conform with Society ethical requirements