Fiber types of human atrophic myofibers with nuclear clumps

During long-standing lower motor neuron (LMN) denervation of human leg muscles muscle fibers are known to disappear, substituted by adipose and fibrous connective tissue. Here we show that in the loose connective tissue that seems to fill the human denervated muscle after five years of lower motor neuron denervation there are many severely atrophic myofibers, which had lost their myofibrillar apparatus and coil distribution of myonuclei that are relocated in clumps (myonuclear clumps). Immunohistochemistry with anti MHCslow and MHCemb shows that some of these severely atrophic myofibers are of slow type, thus demonstrating that they are surviving adults fibers. The contribution of regenerative myogenesis demonstrated in long-lasting LMN denervation may contribute to extend the presence of muscle fibers and of the severely atrophic muscle fibers with nuclear clumps. These results demonstrate that the human muscle fibers survive permanent lower motor neuron denervation much longer than generally accepted and provide the rationale to plan research aimed to recover long-lasting denervated muscle by combining molecular and cellular approaches with functional electrical stimulation.