NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY STUDY OF MUSCLE GROWTH, MDX DYSTROPHY AND GLUCOCORTICOID TREATMENTS - CORRELATION WITH REPAIR

Proton nuclear magnetic resonance spectroscopy (H-1 NMR) can be used t o study skeletal muscle metabolism. The mdx mouse is a unique animal f or studies of muscle regeneration, and models the disease of Duchenne muscular dystrophy (DMD). The goals of this study were to determine th e potential of H-1 NMR spectroscopy as an alternative to conventional histology in monitoring: (1) normal growth in control muscle and the p rogression of dystrophy in mdx muscle, and (2) beneficial treatments ( glucocorticoids) on mdx dystrophy. Ex vivo H-1 NMR spectra of limb and diaphragm muscles were obtained from different ages of control and md r mice, and from mice which were treated with prednisone or deflazacor t. Peaks with contributions from creatine, taurine and lipids were exa mined. Lower levels of taurine and creatine characterized predystrophy and active dystrophy intervals in mdr muscle compared to control. Lev els of taurine increased with stabilization of the disease by repair. A measure of accumulated muscle repair, fiber centronucleation and man y spectral peaks were highly and significantly correlated. Greater amo unts of lipids were found in the diaphragm compared to limb spectra. T reatment of dystrophy, which improved muscle phenotype, resulted in gr eater levels of taurine and creatine, especially in the limb muscle. T herefore, H-1 NMR differentially discriminates: (1) control and mdx mu scle; (2) the progression of mdr dystrophy and developmental stages in normal growth; (3) mild and severe dystrophic phenotypes (diaphragm v s limb); and (4) changes associated with improved muscle phenotype and regeneration (due to treatment or injury). The results focus on monit oring muscle repair, not degeneration. We conclude that H-1 NMR is a r eliable tool in the objective investigation of muscle repair status du ring muscular dystrophy. (C) 1998 John Wiley & Sons, Ltd.