scholarly journals Effects of Zusanli and Ashi Acupoint Electroacupuncture on Repair of Skeletal Muscle and Neuromuscular Junction in a Rabbit Gastrocnemius Contusion Model

2016 ◽  
Vol 2016 ◽  
pp. 1-11
Author(s):  
Zhan-ge Yu ◽  
Rong-guo Wang ◽  
Cheng Xiao ◽  
Jun-yun Zhao ◽  
Qian Shen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Neuromuscular Junction ◽  
Neuromuscular Junctions ◽  
Muscle Repair ◽  
Neuregulin 1 ◽  
Treatment Groups ◽  
Differentiation Factor ◽  
The Mean ◽  
Muscle Specific Kinase

Objective. To explore the effects of electroacupuncture (EA) at ST36 (EA-ST36) and at Ashi acupoints (EA-Ashi) on skeletal muscle repair.Methods. Seventy-five rabbits were randomly divided into five groups: normal, contusion, EA-Ashi, EA-ST36, and EA at Ashi acupoints and ST36 (EA-AS). EA (0.4 mA, 2 Hz, 15 min) was applied after an acute gastrocnemius contusion. The morphology of myofibers and neuromuscular junctions (NMJs) and expressions of growth differentiation factor-8 (GDF-8), acetylcholinesterase (AChE), Neuregulin 1 (NGR1), and muscle-specific kinase (MuSK) were assessed 7, 14, and 28 days after contusion.Results. Compared with that in contusion group, there was an increase in the following respective parameters in treatment groups: the number and diameter of myofibers, the mean staining area, and continuities of NMJs. A comparison of EA-Ashi and EA-ST36 groups indicated that average myofiber diameter, mean staining area of NMJs, and expressions of AChE and NRG1 were higher in EA-Ashi group, whereas expression of GDF-8 decreased on day 7. However, increases in myofiber numbers, expressions of MuSK and AChE, as well as decreases in GDF-8 expression, and the discontinuities were observed in EA-ST36 group on the 28th day.Conclusion. Both EA-ST36 and EA-Ashi promoted myofiber regeneration and restoration of NMJs. EA-Ashi was more effective at earlier stages, whereas EA-ST36 played a more important role at later stages.

scholarly journals The gut microbiota influences skeletal muscle mass and function in mice

2019 ◽  
Vol 11 (502) ◽  
pp. eaan5662 ◽  
Author(s):  
Shawon Lahiri ◽  
Hyejin Kim ◽  
Isabel Garcia-Perez ◽  
Musarrat Maisha Reza ◽  
Katherine A. Martin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Neuromuscular Junction ◽  
Gut Microbiota ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Neuromuscular Junctions ◽  
Short Chain Fatty Acids ◽  
Germ Free ◽  
Mouse Skeletal Muscle ◽  
And Function

The functional interactions between the gut microbiota and the host are important for host physiology, homeostasis, and sustained health. We compared the skeletal muscle of germ-free mice that lacked a gut microbiota to the skeletal muscle of pathogen-free mice that had a gut microbiota. Compared to pathogen-free mouse skeletal muscle, germ-free mouse skeletal muscle showed atrophy, decreased expression of insulin-like growth factor 1, and reduced transcription of genes associated with skeletal muscle growth and mitochondrial function. Nuclear magnetic resonance spectrometry analysis of skeletal muscle, liver, and serum from germ-free mice revealed multiple changes in the amounts of amino acids, including glycine and alanine, compared to pathogen-free mice. Germ-free mice also showed reduced serum choline, the precursor of acetylcholine, the key neurotransmitter that signals between muscle and nerve at neuromuscular junctions. Reduced expression of genes encoding Rapsyn and Lrp4, two proteins important for neuromuscular junction assembly and function, was also observed in skeletal muscle from germ-free mice compared to pathogen-free mice. Transplanting the gut microbiota from pathogen-free mice into germ-free mice resulted in an increase in skeletal muscle mass, a reduction in muscle atrophy markers, improved oxidative metabolic capacity of the muscle, and elevated expression of the neuromuscular junction assembly genes Rapsyn and Lrp4. Treating germ-free mice with short-chain fatty acids (microbial metabolites) partly reversed skeletal muscle impairments. Our results suggest a role for the gut microbiota in regulating skeletal muscle mass and function in mice.

scholarly journals Targeting of the ETS Factor Gabpα Disrupts Neuromuscular Junction Synaptic Function

2007 ◽  
Vol 27 (9) ◽  
pp. 3470-3480 ◽  
Author(s):  
Debra A. O'Leary ◽  
Peter G. Noakes ◽  
Nick A. Lavidis ◽  
Ismail Kola ◽  
Paul J. Hertzog ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factor ◽  
Neuromuscular Junction ◽  
Acetylcholine Receptor ◽  
Neuromuscular Junctions ◽  
Binding Protein ◽  
Synaptic Function ◽  
Single Point Mutation ◽  
Structural Formation ◽  
Ga Binding Protein

ABSTRACT The GA-binding protein (GABP) transcription factor has been shown in vitro to regulate the expression of the neuromuscular proteins utrophin, acetylcholine esterase, and acetylcholine receptor subunits δ and ε through the N-box promoter motif (5′-CCGGAA-3′), but its in vivo function remains unknown. A single point mutation within the N-box of the gene encoding the acetylcholine receptor ε subunit has been identified in several patients suffering from postsynaptic congenital myasthenic syndrome, implicating the GA-binding protein in neuromuscular function and disease. Since conventional gene targeting results in an embryonic-lethal phenotype, we used conditional targeting to investigate the role of GABPα in neuromuscular junction and skeletal muscle development. The diaphragm and soleus muscles from mutant mice display alterations in morphology and distribution of acetylcholine receptor clusters at the neuromuscular junction and neurotransmission properties consistent with reduced receptor function. Furthermore, we confirmed decreased expression of the acetylcholine receptor ε subunit and increased expression of the γ subunit in skeletal muscle tissues. Therefore, the GABP transcription factor aids in the structural formation and function of neuromuscular junctions by regulating the expression of postsynaptic genes.

scholarly journals Subtle Neuromuscular Defects in Utrophin-deficient Mice

1997 ◽  
Vol 136 (4) ◽  
pp. 871-882 ◽  
Author(s):  
R. Mark Grady ◽  
John P. Merlie ◽  
Joshua R. Sanes
Keyword(s):  
Skeletal Muscle ◽  
Neuromuscular Junction ◽  
Acetylcholine Receptors ◽  
Cultured Cells ◽  
Neuromuscular Junctions ◽  
Becker Muscular Dystrophy ◽  
Postsynaptic Membrane ◽  
Mutant Mice ◽  
Nonmuscle Cells ◽  
And Behavior

Utrophin is a large cytoskeletal protein that is homologous to dystrophin, the protein mutated in Duchenne and Becker muscular dystrophy. In skeletal muscle, dystrophin is broadly distributed along the sarcolemma whereas utrophin is concentrated at the neuromuscular junction. This differential localization, along with studies on cultured cells, led to the suggestion that utrophin is required for synaptic differentiation. In addition, utrophin is present in numerous nonmuscle cells, suggesting that it may have a more generalized role in the maintenance of cellular integrity. To test these hypotheses we generated and characterized utrophin-deficient mutant mice. These mutant mice were normal in appearance and behavior and showed no obvious defects in muscle or nonmuscle tissue. Detailed analysis, however, revealed that the density of acetylcholine receptors and the number of junctional folds were reduced at the neuromuscular junctions in utrophin-deficient skeletal muscle. Despite these subtle derangements, the overall structure of the mutant synapse was qualitatively normal, and the specialized characteristics of the dystrophin-associated protein complex were preserved at the mutant neuromuscular junction. These results point to a predominant role for other molecules in the differentiation and maintenance of the postsynaptic membrane.

scholarly journals HDAC6 regulates microtubule stability and clustering of AChRs at neuromuscular junctions

2020 ◽  
Vol 219 (8) ◽  
Author(s):  
Alexis Osseni ◽  
Aymeric Ravel-Chapuis ◽  
Jean-Luc Thomas ◽  
Vincent Gache ◽  
Laurent Schaeffer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Neuromuscular Junction ◽  
Relative Stability ◽  
Neuromuscular Junctions ◽  
Postsynaptic Membrane ◽  
Post Translational Modification ◽  
Acetylation Status ◽  
Microtubule Stability ◽  
Hdac6 Inhibitor ◽  
The Stability

Microtubules (MTs) are known to be post-translationally modified at the neuromuscular junction (NMJ), hence increasing their stability. To date however, the function(s) of the dynamic MT network and its relative stability in the formation and maintenance of NMJs remain poorly described. Stabilization of the MT is dependent in part on its acetylation status, and HDAC6 is capable of reversing this post-translational modification. Here, we report that HDAC6 preferentially accumulates at NMJs and that it contributes to the organization and the stability of NMJs. Indeed, pharmacological inhibition of HDAC6 protects against MT disorganization and reduces the size of acetylcholine receptor (AChR) clusters. Moreover, the endogenous HDAC6 inhibitor paxillin interacts with HDAC6 in skeletal muscle cells, colocalizes with AChR aggregates, and regulates the formation of AChR. Our findings indicate that the focal insertion of AChRs into the postsynaptic membrane is regulated by stable MTs and highlight how an MT/HDAC6/paxillin axis participates in the regulation of AChR insertion and removal to control the structure of NMJs.

Denervation, Reinnervation, and Regeneration of Skeletal Muscle

1981 ◽  
Vol 89 (2) ◽  
pp. 192-196 ◽  
Author(s):  
Bruce M. Carlson
Keyword(s):  
Skeletal Muscle ◽  
Neuromuscular Junction ◽  
Functional Ability ◽  
De Novo ◽  
Neuromuscular Junctions ◽  
Original Structure ◽  
De Novo Synthesis ◽  
Regenerative Capacity ◽  
Neuromuscular Synapses ◽  
Motor End Plate

This paper reviews the responses of skeletal muscle tissue to denervation, with emphasis on the area of neuromuscular junction. In reinnervation, neuromuscular synapses are formed preferentially at the site of the old motor end plate, but the de novo synthesis of new neuromuscular junctions is possible. Skeletal muscle has a good regenerative capacity, and a regenerating muscle fiber can, essentially, return to original structure and functional ability.

scholarly journals Loss of adult skeletal muscle stem cells drives age-related neuromuscular junction degeneration

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Wenxuan Liu ◽  
Alanna Klose ◽  
Sophie Forman ◽  
Nicole D Paris ◽  
Lan Wei-LaPierre ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Neuromuscular Junction ◽  
Neuromuscular Junctions ◽  
Aged Mouse ◽  
Muscle Stem Cell ◽  
Adult Skeletal Muscle ◽  
Muscle Stem Cells ◽  
Age Related

Neuromuscular junction degeneration is a prominent aspect of sarcopenia, the age-associated loss of skeletal muscle integrity. Previously, we showed that muscle stem cells activate and contribute to mouse neuromuscular junction regeneration in response to denervation (Liu et al., 2015). Here, we examined gene expression profiles and neuromuscular junction integrity in aged mouse muscles, and unexpectedly found limited denervation despite a high level of degenerated neuromuscular junctions. Instead, degenerated neuromuscular junctions were associated with reduced contribution from muscle stem cells. Indeed, muscle stem cell depletion was sufficient to induce neuromuscular junction degeneration at a younger age. Conversely, prevention of muscle stem cell and derived myonuclei loss was associated with attenuation of age-related neuromuscular junction degeneration, muscle atrophy, and the promotion of aged muscle force generation. Our observations demonstrate that deficiencies in muscle stem cell fate and post-synaptic myogenesis provide a cellular basis for age-related neuromuscular junction degeneration and associated skeletal muscle decline.

scholarly journals Functional Monitoring after Trabeculectomy or XEN Microstent Implantation Using Spectral Domain Optical Coherence Tomography and Visual Field Indices—A Retrospective Comparative Cohort Study

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 273
Author(s):  
Marc Schargus ◽  
Catharina Busch ◽  
Matus Rehak ◽  
Jie Meng ◽  
Manuela Schmidt ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Cohort Study ◽  
Visual Field ◽  
Spectral Domain ◽  
Optical Coherence ◽  
Treatment Groups ◽  
Rnfl Thickness ◽  
Comparative Cohort Study ◽  
The Mean ◽  
All Treatment

The aim of this study was to compare the efficacy of trabeculectomy (TE), single XEN microstent implantation (solo XEN) or combined XEN implantation and cataract surgery (combined XEN) in primary open-angle glaucoma cases, naïve to prior surgical treatment, using a monocentric retrospective comparative cohort study. Intraocular pressure (IOP) and the number of IOP-lowering drugs (Meds) were monitored during the first 24 months after surgery. Further disease progression was monitored using peripapillary retinal nerve fiber layer (RNFL) thickness examinations using spectral domain optical coherence tomography (OCT) as well as visual acuity (VA) and visual field (VF) tests. In the TE group (52 eyes), the mean IOP decreased from 24.9 ± 5.9 to 13.9 ± 4.2 mmHg (p < 0.001) and Meds decreased from 3.2 ± 1.2 to 0.5 ± 1.1 (p < 0.001). In the solo XEN (38 eyes) and the combined XEN groups, the mean IOP decreased from 24.1 ± 4.7 to 15.7 ± 3.0 mmHg (p < 0.001) and 25.4 ± 5.6 to 14.7 ± 3.2 mmHg (p < 0.001), while Meds decreased from 3.3 ± 0.8 to 0.8 ± 1.2 (p < 0.001) and 2.7 ± 1.2 to 0.4 ± 1.0 (p < 0.001), respectively. The VF and VA indices showed no sign of further deterioration, the RNFL thickness further decreased in all treatment groups after surgery. TE and XEN led to comparable reductions in IOP and Meds. Although the VA and VF indices remained unaltered, the RNFL thickness continuously decreased in all treatment groups during the 24-month follow-up.

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