Nuclear magnetic resonance spectroscopy study of muscle growth, mdx dystrophy and glucocorticoid treatments: correlation with repair.
Proton nuclear magnetic resonance spectroscopy (1H NMR) can be used to study skeletal muscle metabolism. The mdx mouse is a unique animal for studies of muscle regeneration, and models the disease of Duchenne muscular dystrophy (DMD). The goals of this study were to determine the potential of 1H NMR spectroscopy as an alternative to conventional histology in monitoring: (1) normal growth in control muscle and the progression of dystrophy in mdx muscle, and (2) beneficial treatments (glucocorticoids) on mdx dystrophy. Ex vivo 1H NMR spectra of limb and diaphragm muscles were obtained from different ages of control and mdx mice, and from mice which were treated with prednisone or deflazacort. Peaks with contributions from creatine, taurine and lipids were examined. Lower levels of taurine and creatine characterized predystrophy and active dystrophy intervals in mdx muscle compared to control. Levels of taurine increased with stabilization of the disease by repair. A measure of accumulated muscle repair, fiber centronucleation and many spectral peaks were highly and significantly correlated. Greater amounts of lipids were found in the diaphragm compared to limb spectra. Treatment of dystrophy, which improved muscle phenotype, resulted in greater levels of taurine and creatine, especially in the limb muscle. Therefore, 1H NMR differentially discriminates: (1) control and mdx muscle; (2) the progression of mdx dystrophy and developmental stages in normal growth; (3) mild and severe dystrophic phenotypes (diaphragm vs limb); and (4) changes associated with improved muscle phenotype and regeneration (due to treatment or injury). The results focus on monitoring muscle repair, not degeneration. We conclude that 1H NMR is a reliable tool in the objective investigation of muscle repair status during muscular dystrophy.
McIntosh
L
L
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada.
Granberg
K E
KE
Brière
K M
KM
Anderson
J E
JE
D000818:Animals; D016002:Discriminant Analysis; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development* / Q000528:radiation effects; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype; D011241:Prednisone / Q000627:therapeutic use*; D011282:Pregnenediones / Q000627:therapeutic use*; D012038:Regeneration
D011282:Pregnenediones; C021988:deflazacort; D011241:Prednisone