This study was performed to determine whether there are distinctive features to the pattern of muscle denervation in motor neuron disease. We first compared muscle biopsies from patients with amyotrophic lateral sclerosis (ALS) or Kennedy's disease with other causes of denervation. Groups of atrophic muscle fibers, with individual groups containing both fiber types I and II, occurred frequently in motor neuron disease but not other causes of denervation. We then identified 11 additional muscle biopsies with frequent atrophic groups containing mixed fiber types. Chart review revealed that 10 patients had a final diagnosis of motor neuron disease or ALS and one had multifocal motor neuropathy. We conclude that muscle biopsy may have diagnostic utility early in the course of motor neuron disease. The muscle biopsy pattern of frequent atrophic groups containing mixed fiber types should suggest a diagnosis of a motor neuron syndrome or motor neuropathy.
"ated to occur when denervated myofibers are reinnervated by collateral sprouts from neighboring axons ( Andersen et al . , 1996 ; Fischer et al . , 2004 ; Schaefer et al . , 2005 ; Soraru et al . , 2008 ) . On the other hand , it has also been reported that muscle biopsies from ALS patients exhibit muscle fiber atrophy but no fiber type grouping ( Baloh et al . , 2007 ) . The reason for this seeming discrepancy is not apparent from the data available , but ALS actually encompasses a spectrum of disorders , and it is possible that fiber type grouping occurs in some forms of the disease and not others ( Soraru et al . , 2008 ) . Because no type grouping in intercostal muscle ( this study ) or in pelvic"
"Further, in Sod1 À/À mice, measurements of steady state redox potential of glutathione (which is routinely used as indicator of the intracellular redox state) in tibial nerve and gastrocnemius muscle showed a selective involvement of the nerve at 4 months, again indicating the primary involvement of the axon (Fischer et al., 2012). Thus muscle changes in Sod1 À/À mice are secondary to denervation; they are non-specific and also present in muscle biopsies from patients with ALS (Baloh et al., 2007a). "
[Show abstract][Hide abstract] ABSTRACT: Mutations in the gene superoxide dismutase 1 (SOD1) are causative for familial forms of the neurodegenerative disease amyotrophic lateral sclerosis. When the first SOD1 mutations were identified they were postulated to give rise to amyotrophic lateral sclerosis through a loss of function mechanism, but experimental data soon showed that the disease arises from a-still unknown-toxic gain of function, and the possibility that loss of function plays a role in amyotrophic lateral sclerosis pathogenesis was abandoned. Although loss of function is not causative for amyotrophic lateral sclerosis, here we re-examine two decades of evidence regarding whether loss of function may play a modifying role in SOD1-amyotrophic lateral sclerosis. From analysing published data from patients with SOD1-amyotrophic lateral sclerosis, we find a marked loss of SOD1 enzyme activity arising from almost all mutations. We continue to examine functional data from all Sod1 knockout mice and we find obvious detrimental effects within the nervous system with, interestingly, some specificity for the motor system. Here, we bring together historical and recent experimental findings to conclude that there is a possibility that SOD1 loss of function may play a modifying role in amyotrophic lateral sclerosis. This likelihood has implications for some current therapies aimed at knocking down the level of mutant protein in patients with SOD1-amyotrophic lateral sclerosis. Finally, the wide-ranging phenotypes that result from loss of function indicate that SOD1 gene sequences should be screened in diseases other than amyotrophic lateral sclerosis.
"We next examined the histological properties of skeletal muscle from Actb-MNsKO mice for subtle or early signs of denervation. In a number of motor neuron diseases, selective loss of a particular fiber type or fiber type clustering can occur and is consistent with early motor neuron degeneration –. We stained gastrocnemius muscle sections from control and Actb-MNsKO mice at 6 and 12 months of age with antibodies to fast and slow myosin heavy chain to label fast and slow twitch muscle fibers respectively. "
[Show abstract][Hide abstract] ABSTRACT: The proper localization of ß-actin mRNA and protein is essential for growth cone guidance and axon elongation in cultured neurons. In addition, decreased levels of ß-actin mRNA and protein have been identified in the growth cones of motor neurons cultured from a mouse model of Spinal Muscular Atrophy (SMA), suggesting that ß-actin loss-of-function at growth cones or pre-synaptic nerve terminals could contribute to the pathogenesis of this disease. However, the role of ß-actin in motor neurons in vivo and its potential relevance to disease has yet to be examined. We therefore generated motor neuron specific ß-actin knock-out mice (Actb-MNsKO) to investigate the function of ß-actin in motor neurons in vivo. Surprisingly, ß-actin was not required for motor neuron viability or neuromuscular junction maintenance. Skeletal muscle from Actb-MNsKO mice showed no histological indication of denervation and did not significantly differ from controls in several measurements of physiologic function. Finally, motor axon regeneration was unimpaired in Actb-MNsKO mice, suggesting that ß-actin is not required for motor neuron function or regeneration in vivo.
PLoS ONE 03/2011; 6(3):e17768. DOI:10.1371/journal.pone.0017768 · 3.23 Impact Factor
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