scholarly journals Satellite Cells and Neuromuscular Spindles in Long Term Denervated Skeletal Muscles

Author(s):  
André Luis Shinohara ◽  
Carina Melo ◽  
Farooque Ahmed ◽  
Beatriz Sangalette ◽  
João Vitor Shindo ◽  
...  

Abstract Satellite cells (SC) are quiescent cell located between the sarcolemma and basal lamina of the skeletal muscle fibers. The SC can get activated contributing to regeneration and/or growth of muscle. The neuromuscular spindles are mechanoreceptors located within the skeletal muscle and are considered as contractile regulatory unit. It is composed of intrafusal muscle fibers (IF), surrounded by a sheath and is parallel to extrafusal fibers. Denervation cause changes in skeletal muscles both in the SC and neuromuscular spindles. This study analyzed quantitatively the IF and SC in Wistar rats denervated for long period. The animals were divided into normal and denervated groups. The soleus and extensor longus digitorum longus were denervated experimentally during periods of 0, 12, 16, 19, 30 and 38 weeks. The percentage of SC immediately after denervation increases when compared to normal group and later decreases in both the groups. During the process of denervation, there was an increase in IF when compared with normal group. The percentage of SC reduces significantly between the periods of denervation in both the groups. The smaller percentage of SC corresponds to higher number of IF. Besides that the number of SC decreases after denervation. As for IF, with the increase in time in normal group, the number of fibers was unaltered. However, in the experimental group, with increase in the time of denervation, the percentage of SC decreases while there is increase in the number of IF significantly. In denervated muscles for long period, there is decrease in the percentage of SC and increase in IF. Our results suggest that the period between 16th and 19th week post denervation is the best time for reinnervation of denervated muscle.

Author(s):  
Leonardo Hernández

The influence of Ca2+ and other divalent cations on contractile responses of slow skeletal muscle fibers of the frog (Rana pipiens) under conditions of chronic denervation was investigated.Isometric tension was recorded from slow bundles of normal and denervated cruralis muscle in normal solution and in solutions with free calcium concentration solution or in solutions where other divalent cations (Sr2+, Ni2+, Co2+ or Mn2+) substituted for calcium. In the second week after nerve section, in Ca2+-free solutions, we observed that contractures (evoked from 40 to 80 mM-K+) of non-denervated muscles showed significantly higher tensions (p<0.05), than those from denervated bundles. Likewise, in solutions where calcium was substituted by all divalent cations tested, with exception of Mn2+, the denervated bundles displayed lower tension than non-denervated, also in the second week of denervation. In this case, the Ca2+ substitution by Sr2+ caused the higher decrease in tension, followed by Co2+ and Ni2+, which were different to non-denervated bundles, as the lowest tension was developed by Mn2+, followed by Co2+, and then Ni2+ and Sr2+. After the third week, we observed a recovery in tension. These results suggest that denervation altering the binding capacity to divalent cations of the voltage sensor.


2022 ◽  
Author(s):  
Sanzana Hoque ◽  
Marie Sjogren ◽  
Valerie Allamand ◽  
Kinga Gawlik ◽  
Naomi Franke ◽  
...  

Huntington's disease (HD) is caused by CAG repeat expansion in the huntingtin (HTT) gene. Skeletal muscle wasting alongside central pathology is a well-recognized phenomenon seen in patients with HD and HD mouse models. HD muscle atrophy progresses with disease and affects prognosis and quality of life. Satellite cells, progenitors of mature skeletal muscle fibers, are essential for proliferation, differentiation, and repair of muscle tissue in response to muscle injury or exercise. In this study, we aim to investigate the effect of mutant HTT on the differentiation and regeneration capacity of HD muscle by employing in vitro mononuclear skeletal muscle cell isolation and in vivo acute muscle damage model in R6/2 mice. We found that, similar to R6/2 adult mice, neonatal R6/2 mice also exhibit a significant reduction in myofiber width and morphological changes in gastrocnemius and soleus muscles compared to WT mice. Cardiotoxin (CTX)-induced acute muscle damage in R6/2 and WT mice showed that the Pax7+ satellite cell pool was dampened in R6/2 mice at 4 weeks post-injection, and R6/2 mice exhibited an altered inflammatory profile in response to acute damage. Our results suggest that, in addition to the mutant HTT degenerative effects in mature muscle fibers, expression of mutant HTT in satellite cells might alter developmental and regenerative processes to contribute to the progressive muscle mass loss in HD. Taken together, the results presented here encourage further studies evaluating the underlying mechanisms of satellite cell dysfunction in HD mouse models.


1996 ◽  
Vol 199 (11) ◽  
pp. 2359-2367
Author(s):  
C Brösamle ◽  
D P Kuffler

The vertebrate neuromuscular junction is a highly specialized structure containing many unique proteins and an underlying cluster of nuclei. Part of this specialization results from the expression of the genes for these proteins in nuclei clustered in the postsynaptic region. Contractile activity, as well as molecules located in the synaptic extracellular matrix (ECM), have been implicated in the induction of gene expression in these clustered nuclei. The present experiments were aimed at examining whether the presence of the synaptic ECM and presynaptic cells play a role in maintaining the clustering of the nuclei. We describe the normal distribution of nuclei clustered in the synaptic region of intact adult frog, Rana pipiens, skeletal muscle fibers and show that innervation is not required to maintain the nuclear clusters. Even after long-term (4 week) denervation, the clusters remain unchanged. Dissociation of the muscle fibers with proteases that remove ECM, Schwann cells and other satellite cells from the synaptic sites is followed by a rapid (within approximately 1.5 h) and almost complete dispersal of the clustered nuclei. Attempts to recluster the postsynaptic nuclei by the application of ECM components to muscle fibers in vitro were not successful. We propose that a factor or factors, localized in the synaptic ECM as a result of synapse formation and acting via the transmembrane or cytoplasmic domains of their respective receptors, induces the formation of a specialized cytoskeleton in the postsynaptic region that is capable of pulling in or 'trapping' nuclei. The removal of these factors from the ECM by proteases brings about the disorganization of the cytoskeleton and the freeing of the 'trapped' nuclei.


1997 ◽  
Vol 272 (5) ◽  
pp. C1420-C1428 ◽  
Author(s):  
A. Nori ◽  
K. A. Nadalini ◽  
A. Martini ◽  
R. Rizzuto ◽  
A. Villa ◽  
...  

Calsequestrin (CS) is the junctional sarcoplasmic reticulum (jSR) Ca2+ binding protein responsible for intraluminal Ca2+ storage. The targeting mechanisms of CS to the jSR are yet to be unraveled. The nine-amino acid epitope of the influenza virus hemoagglutinin (referred to as HA1) was added at the COOH-terminal of CS by polymerase chain reaction cloning. The HA1-tagged CS cDNA was transiently transfected in either HeLa cells, myogenic cell lines, such as C2 and L8 cells, myoblasts of rat skeletal muscle primary cultures, or regenerating soleus muscle fibers of adult rats. The expression and intracellular localization of chimeric CS-HA1 were monitored by epifluorescence and confocal microscopy using either anti-CS antibodies or anti-HA1 antibodies. About 30% of transfected HeLa cells and 20-40% of myogenic cells expressed CS-HA1 into intracellular compartments, such as the perinuclear cisternae of endoplasmic reticulum (ER). Myoblasts of newborn rat skeletal muscles were first transfected and subsequently stimulated to differentiate into myotubes. CS-HA1 was detected in approximately 20% of transfected myotubes and did not affect CS distribution in myotubes. In the soleus muscle of adult rat, intramuscular injection of bupivacaine induced necrosis followed by regeneration. In vivo transfection of HA1-tagged CS cDNA in regenerating skeletal muscles determined expression in a few skeletal muscle fibers; CS-HA1 was localized only in jSR, as judged by confocal microscopy of longitudinal sections. The present results show that chimeric CS-HA1 is correctly sorted to ER/SR compartments and that the free COOH-terminal is not requested for sorting, retention, and segregation of CS to the SR.


2020 ◽  
Vol 318 (6) ◽  
pp. C1178-C1188 ◽  
Author(s):  
Davis A. Englund ◽  
Kevin A. Murach ◽  
Cory M. Dungan ◽  
Vandré C. Figueiredo ◽  
Ivan J. Vechetti ◽  
...  

To date, studies that have aimed to investigate the role of satellite cells during adult skeletal muscle adaptation and hypertrophy have utilized a nontranslational stimulus and/or have been performed over a relatively short time frame. Although it has been shown that satellite cell depletion throughout adulthood does not drive skeletal muscle loss in sedentary mice, it remains unknown how satellite cells participate in skeletal muscle adaptation to long-term physical activity. The current study was designed to determine whether reduced satellite cell content throughout adulthood would influence the transcriptome-wide response to physical activity and diminish the adaptive response of skeletal muscle. We administered vehicle or tamoxifen to adult Pax7-diphtheria toxin A (DTA) mice to deplete satellite cells and assigned them to sedentary or wheel-running conditions for 13 mo. Satellite cell depletion throughout adulthood reduced balance and coordination, overall running volume, and the size of muscle proprioceptors (spindle fibers). Furthermore, satellite cell participation was necessary for optimal muscle fiber hypertrophy but not adaptations in fiber type distribution in response to lifelong physical activity. Transcriptome-wide analysis of the plantaris and soleus revealed that satellite cell function is muscle type specific; satellite cell-dependent myonuclear accretion was apparent in oxidative muscles, whereas initiation of G protein-coupled receptor (GPCR) signaling in the glycolytic plantaris may require satellite cells to induce optimal adaptations to long-term physical activity. These findings suggest that satellite cells play a role in preserving physical function during aging and influence muscle adaptation during sustained periods of physical activity.


2005 ◽  
Vol 83 (5) ◽  
pp. 674-676 ◽  
Author(s):  
Ashley C Wozniak ◽  
Judy E Anderson

The activity of satellite cells during myogenesis, development, or skeletal muscle regeneration is strongly modelled using cultures of single muscle fibers. However, there are variations in reported features of gene or protein expression as examined with single-fiber cultures. Here, we examined the potential differences in activation of satellite cells on normal mouse muscle fibers produced during a standard isolation protocol, with or without agitation during collagenase digestion. Activation was detected in satellite cells on fibers after 24 and 48 h of culture in basal growth medium using immunodetection of the incorporation of bromodeoxyuridine (BrdU) into DNA and quantification of the number of BrdU-positive cells per fiber. After 24 and 48 h in culture under nonactivating conditions, the number of activated (BrdU+) satellite cells was greater on fibers that had received gentle agitation during collagenase digestion than on those that were subject to digestion without agitation during isolation. The findings are interpreted to mean that at least some of the variation among published reports may derive from the application of various methods of fiber isolation. The information should be useful for maintaining satellite cell quiescence during studies of the regulatory steps that lead to satellite cell activation.Key words: activation, skeletal muscle, proliferation, single-fiber culture, myogenesis.


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