Myogenesis in human denervated muscle biopsies

Abstract

Electron microscopic studies of long-term denervated rat muscles have identified very small, immature myofibers that are believed to arise from detached satellite cells that have fused to form new fibers within the interstitial space. At present, it is unknown whether and to what extent equivalent fibers exist in denervated human muscle. Serial sections of muscle biopsies from 66 patients diagnosed with polyneuropathy or amyotrophic lateral sclerosis were immunolabeled with anti-NCAM and antineonatal myosin heavy chain monoclonal antibodies that are both neurally and developmentally regulated. We evaluated 200 myofibers in each section. Of the biopsy specimens, 75% contained small myofibers that showed a thin perinuclear cytoplasmic rim. Small fibers expressing neonatal myosin heavy chain (MHCnϩ) were found in all of these biopsies (100%) and NCAMϩ fibers in 98%. The percentage of MHCnϩ small fibers averaged 82% and NCAMϩ small myofibers averaged 40%. The percentage of NCAMϩ small fibers was significantly lower than that of MHCnϩ fibers. In contrast, the percentage of MHCnϩ vs. NCAMϩ angular atrophic fibers did not show a significant difference. A substantial subset of neurogenic biopsies showed small fibers that differ from angular atrophic fibers both in size and expression pattern of MHCn and NCAM. Myogenesis appears to be a frequent finding in neurogenic atrophy.

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

“…4B). Our observation of the angular profiles of the atrophic PD muscle fibers is in line with the previous studies reporting the morphological characteristics for skeletal muscle atrophy (Sakkas et al, 2003;Doppler et al, 2008;Pandey et al, 2012;Hara et al, 2013;Werneck et al, 2013). Additionally, muscle atrophy indicated by significant decline in muscle fiber cross-sectional area (Figs.…”

Physiological characterization of human muscle acetylcholine receptors from ALS patients

“…In this study we used two different technical approaches, both of which showed that riluzole, at clinically relevant doses, can block the ACh-evoked currents in ALS patients as well as in denervated patients. Because ongoing myogenesis has been reported in muscle biopsies of ALS or traumatically denervated patients (36), innervation of newly formed muscle fibers likely proceeds alongside reinnervation of old fibers by surviving motor neurons in ALS patients. The activity of AChRs plays a role in both processes.…”

NF-κB–mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia

“…This is analogous to a condition of insulin resistance whereby Akt signaling is inhibited and protein synthesis is reduced, leading to unregulated proteolysis. Whether such a similar mechanism underlies wasting in other atrophy conditions was not explored, but findings from denervation and disuse models argue against such a notion, since in these models satellite cell number decline (9)(10)(11) as opposed to increasing, as observed under a tumor burden. In addition, although our results demonstrated that myogenin was not induced during cancer cachexia, its expression was previously reported to be highly elevated in denervation and required for activation of the ubiquitin proteasome system (63).…”

“…Since the discovery of the satellite cell (8), numerous dynamic processes involving these cells have been associated with various atrophy conditions. In denervation, satellite cell numbers decline, and over time, small new immature fibers form in the interstitial space, potentially resulting from an abortive myogenic program (9,10). In disuse atrophy, the mitotic activity of satellite cells is reduced (11), while in cancer, chronic obstructive pulmonary disease, renal failure, and burn-induced cachexia, the expression of myogenic factors has previously been described (12)(13)(14)(15), and in some cases was linked to dysregulated differentiation and muscle loss (13,16,17).…”