G.P.200: The expression profile of developmental markers in diagnostic muscle biopsies indicates the presence of a “neurogenic muscle regeneration”

Abstract

In standard muscle biopsy investigation regenerating fibers are commonly seen in dystrophic muscle, but not in neurogenic myopathy. Using immunohistochemistry these disease groups do differ in the expression of embryonic and fetal myosin heavy chain, but the significance of this is unknown. To learn more about regenerating processes in these groups we investigated the expression of several markers of satellite cells in different stages of activation, and of embryonic and fetal myosin heavy chain in muscle biopsies from patients with dystrophy and neurogenic myopathy, as well as in controls. Frozen sections from 10 patients with limb-girdle muscle dystrophies, 10 patients with motor neuron disease, 10 young and 10 elderly age matched control patients were selected. Immunohistological staining using following antibodies was performed: PAX7, N-CAM, MyoD1, myogenin, neonatal myosin heavy chain, developmental myosin heavy chain and spectrin. The same area in adjacent sections was photographed, followed by counting of fibers and satellite cells. The quotient of myogenin and PAX7 was used as an index for satellite cell activation, and the expressions of the variants of myosin heavy chain were compared between the groups. All biopsies were from the anterior tibial muscle. We found a significantly higher index of activated satellite cells in neurogenic myopathy than in dystrophic myopathy or controls. The higher index of satellite cell activation was paralleled by a higher expression of MyoD1 (indicating satellite cell proliferation). Embryonic myosin was more frequent in dystrophic compared to neurogenic myopathy. The parameters were low and did not differ between the young and elderly control biopsies. The results indicate that there is satellite cell activation in neurogenic myopathy exceeding the activation in dystrophies, and that regenerating fibers in this disease group may by pass the stage of expressing embryonic myosin.