Muscular Dystrophy: Centronucleation May Reflect a Compensatory Activation of Defective Myonuclei

Abstract

Muscular dystrophy has long been believed to be characterized by degeneration and abortive regeneration of muscle fibers (the muscle degeneration theory), but unfortunately its pathogenesis is still unclear and an effective treatment has yet to be developed. As a challenge to the theory, we have proposed an alternative muscle-defective-growth theory and a further bone muscle growth imbalance hypothesis supposing possible defects in bone-growth-dependent muscle growth based on our findings in hereditary dystrophic dy mice (C57BL/6J dy/dy). This review presents some new insights into the pathogenesis of the disease along with our hypothesis, focusing on the physiological meaning of centronucleation, one of the major pathological changes commonly observed in dystrophic muscles of man and experimental animals.

Green tea extract decreases muscle pathology and NF-κB immunostaining in regenerating muscle fibers of mdx mice

“…The large percent area of regenerating fibers compared to other histopathological features indicates that the regenerative process is a substantial contributor to dystrophic muscle pathology. Studies detailing the process of muscle regeneration have shown that in damaged muscle tissue, fibers are capable of returning to normal fiber morphology; however, many regenerated fibers retain centrally located nuclei indefinitely 36–39. The persistence of centrally located nuclei is believed to signify that abnormal processes are occurring in these cells that prevent the nuclei from returning to the periphery of the cell 36–39.…”

“…Studies detailing the process of muscle regeneration have shown that in damaged muscle tissue, fibers are capable of returning to normal fiber morphology; however, many regenerated fibers retain centrally located nuclei indefinitely 36–39. The persistence of centrally located nuclei is believed to signify that abnormal processes are occurring in these cells that prevent the nuclei from returning to the periphery of the cell 36–39. From this initial analysis, it was determined that for the GTE treatments muscle pathology should be examined at ages 28 and 42 days because these time points represent the early degenerative and regenerative disease stages.…”