Effects of eccentric training on the skeletal muscle of mdx mice after long period of training. morphological and functional evaluations

Abstract

Duchene Muscular Dystrophy (DMD) is a recessive degenerative disease linked to the X chromosome. DMD is caused by the absence of the protein dystrophin, which is essential for muscle integrity. A lack of dystrophin leads to muscle weakness and progressive degeneration, and eventually to death due to respiratory failure. These alterations can be determined by changes of the amount of myosin heavy chain (MHC) in dystrophic muscles and, vital muscles as diaphragm can become fatigable. Eccentric exercise has been used to revert or minimize the morphological and functional alterations observed in dystrophic muscles. In this project we propose to analyze the effects of eccentric exercise over different fiber types and quantify the alterations in active force of single permeabilized fibers. Methods: Male mice (mean of age between 4-6 weeks old) will be divided into four groups: (i) mdx sedentary; (ii) mdx trained in treadmill running; (iii) wild type sedentary; (iv) wild type trained in treadmill running. Each group will be further divided into two subgroups according to the training duration: 3 days and 36 days. After the training sessions, animals will be euthanized, and fragments of muscles will be removed for different analyses. To identify different types of fibers will be used immunofluorescence technique. Mechanical tests will be performed in both groups and the active force in 2.5um of sarcomere length will be measured. Expected Results: After 3 day of eccentric training will be expected an increase of pathological alterations in dystrophic muscles without significant changes in the different fiber types and in the force contraction. In another hand, after thirty six days of training, will be expected to find signals of cellular regeneration in dystrophic muscles accompanied by alterations in the different fiber types and an increase of the force contraction of singles cells. (AU)