RESUMEN
AIMS: Increasing evidences suggest a similarity in the pathophysiological mechanisms of neuronal cell death in amyotrophic lateral sclerosis (ALS) and myofibre degeneration in sporadic inclusion body myositis (sIBM). The aim of this study is to elucidate the involvement of ALS-causing proteins in the pathophysiological mechanisms in sIBM. METHODS: Skeletal muscle biopsy specimens of five patients with sIBM, two with oculopharyngeal muscular dystrophy (OPMD), three with polymyositis (PM), three with dermatomyositis (DM), three with neurogenic muscular atrophy, and three healthy control subjects were examined. We analysed the expression and localization of familial ALS-causing proteins, including transactive response DNA binding protein-43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), Cu/Zn superoxide dismutase (SOD1) and optineurin (OPTN) by immunohistochemistry. RESULTS: TDP-43, OPTN and, to a lesser extent, FUS/TLS were more frequently accumulated in the cytoplasm in patients with sIBM and OPMD than in patients with PM, DM, neurogenic muscular atrophy, or healthy control subjects. SOD1 was accumulated in a small percentage of myofibres in patients with sIBM and OPMD, and to a very small extent in patients with PM and DM. Confocal microscopy imaging showed that TDP-43 proteins more often colocalized with OPTN than with FUS/TLS, p62 and phosphorylated Tau. CONCLUSIONS: These findings suggest that OPTN in cooperation with TDP-43 might be involved in the pathophysiological mechanisms of skeletal muscular degeneration in myopathy with rimmed vacuoles. Further investigation into these mechanisms is therefore warranted.
Asunto(s)
Proteínas de Unión al ADN/fisiología , Miositis por Cuerpos de Inclusión/genética , Miositis por Cuerpos de Inclusión/patología , Proteinopatías TDP-43/genética , Proteinopatías TDP-43/patología , Factor de Transcripción TFIIIA/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/patología , Biopsia , Proteínas de Ciclo Celular , Proteínas de Unión al ADN/genética , Dermatomiositis/genética , Dermatomiositis/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Proteínas de Transporte de Membrana , Persona de Mediana Edad , Atrofia Muscular/genética , Atrofia Muscular/patología , Distrofia Muscular Oculofaríngea/genética , Distrofia Muscular Oculofaríngea/patología , Polimiositis/genética , Polimiositis/patología , Proteína FUS de Unión a ARN/metabolismo , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1 , Factor de Transcripción TFIIIA/genéticaRESUMEN
The purpose of this study was to investigate the effect of intensive eccentric exercise on hamstring muscles by using magnetic resonance imaging (MRI) and to elucidate the relationships between the changes in the electromyographic (EMG) parameters and in the transverse relaxation time (T2) of the hamstring muscles. Seven male volunteers performed eccentric knee flexion exercise, and the EMG activity of the hamstring muscles was simultaneously measured. Before and immediately after the exercise, the maximum isometric knee flexion torque was measured and MR images of the hamstring muscles were obtained. For all hamstring muscles, the EMG activity of the fifth set was significantly lower than that of the first set. For each subject, a significant correlation was detected between the percentage change in the value of the post-exercise T2 value and those of EMG signals during the exercise only for the semitendinosus (ST) muscle and not for the biceps femoris (BF) and the semimembranosus (SM) muscles. These results suggested that the EMG-activity reductions in the BF, ST, and SM muscles were due to neuromuscular fatigue, and moreover the reduction in the ST muscle was due to a failure in the E-C coupling, which was caused by excessive muscle-fiber damage.
