Cellular Plasticity of the Neuromuscular System

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 12617

Special Issue Editors

School of Kinesiology and Physical Therapy, University of Central Florida, Orlando, FL 32816, USA
Interests: neuromuscular; exercise; disuse; skeletal muscle; aging
College of William and Mary, Williamsburg, VA 23187, USA
Interests: neuromuscular; exercise; disuse; skeletal muscle; aging

Special Issue Information

Dear Colleagues,

The neuromuscular system is large—comprising ~40% of the body’s entire mass—and vital to our health and well-being. It allows movement, including health-related exercise, as well as normal, yet necessary, activities of daily living. This system is capable of considerable cellular remodeling as a result of natural post-natal development, and aging-related deterioration. Moreover, even in healthy adults significant remodeling of the myofibers, motor neurons, and neuromuscular junctions that these cells join together to form has been demonstrated with scientific inquiry. For example, changes in activity, whether increases via exercise, or decreases, i.e. disuse, elicit significant neuromuscular remodeling. In this special issue of Cells, recognized experts of the neuromuscular system will address cellular remodeling of that system, and how it affects the health and function of the whole organism.

Dr. Matt S. Stock
Prof. Dr. Michael Deschenes
Guest Editors

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Keywords

  • exercise
  • disuse
  • neuromuscular junction
  • motor unit
  • myofiber

Published Papers (5 papers)

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Research

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15 pages, 2022 KiB  
Article
Different Resistance Exercise Loading Paradigms Similarly Affect Skeletal Muscle Gene Expression Patterns of Myostatin-Related Targets and mTORC1 Signaling Markers
by Mason C. McIntosh, Casey L. Sexton, Joshua S. Godwin, Bradley A. Ruple, J. Max Michel, Daniel L. Plotkin, Tim N. Ziegenfuss, Hector L. Lopez, Ryan Smith, Varun B. Dwaraka, Adam P. Sharples, Vincent J. Dalbo, C. Brooks Mobley, Christopher G. Vann and Michael D. Roberts
Cells 2023, 12(6), 898; https://doi.org/10.3390/cells12060898 - 15 Mar 2023
Cited by 3 | Viewed by 3543
Abstract
Although transcriptome profiling has been used in several resistance training studies, the associated analytical approaches seldom provide in-depth information on individual genes linked to skeletal muscle hypertrophy. Therefore, a secondary analysis was performed herein on a muscle transcriptomic dataset we previously published involving [...] Read more.
Although transcriptome profiling has been used in several resistance training studies, the associated analytical approaches seldom provide in-depth information on individual genes linked to skeletal muscle hypertrophy. Therefore, a secondary analysis was performed herein on a muscle transcriptomic dataset we previously published involving trained college-aged men (n = 11) performing two resistance exercise bouts in a randomized and crossover fashion. The lower-load bout (30 Fail) consisted of 8 sets of lower body exercises to volitional fatigue using 30% one-repetition maximum (1 RM) loads, whereas the higher-load bout (80 Fail) consisted of the same exercises using 80% 1 RM loads. Vastus lateralis muscle biopsies were collected prior to (PRE), 3 h, and 6 h after each exercise bout, and 58 genes associated with skeletal muscle hypertrophy were manually interrogated from our prior microarray data. Select targets were further interrogated for associated protein expression and phosphorylation induced-signaling events. Although none of the 58 gene targets demonstrated significant bout x time interactions, ~57% (32 genes) showed a significant main effect of time from PRE to 3 h (15↑ and 17↓, p < 0.01), and ~26% (17 genes) showed a significant main effect of time from PRE to 6 h (8↑ and 9↓, p < 0.01). Notably, genes associated with the myostatin (9 genes) and mammalian target of rapamycin complex 1 (mTORC1) (9 genes) signaling pathways were most represented. Compared to mTORC1 signaling mRNAs, more MSTN signaling-related mRNAs (7 of 9) were altered post-exercise, regardless of the bout, and RHEB was the only mTORC1-associated mRNA that was upregulated following exercise. Phosphorylated (phospho-) p70S6K (Thr389) (p = 0.001; PRE to 3 h) and follistatin protein levels (p = 0.021; PRE to 6 h) increased post-exercise, regardless of the bout, whereas phospho-AKT (Thr389), phospho-mTOR (Ser2448), and myostatin protein levels remained unaltered. These data continue to suggest that performing resistance exercise to volitional fatigue, regardless of load selection, elicits similar transient mRNA and signaling responses in skeletal muscle. Moreover, these data provide further evidence that the transcriptional regulation of myostatin signaling is an involved mechanism in response to resistance exercise. Full article
(This article belongs to the Special Issue Cellular Plasticity of the Neuromuscular System)
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16 pages, 1535 KiB  
Article
Cellular and Subcellular Characteristics of Neuromuscular Junctions in Muscles with Disparate Duty Cycles and Myofiber Profiles
by Michael R. Deschenes, Mia K. Mifsud, Leah G. Patek and Rachel E. Flannery
Cells 2023, 12(3), 361; https://doi.org/10.3390/cells12030361 - 18 Jan 2023
Cited by 1 | Viewed by 1261
Abstract
The neuromuscular system accounts for a large portion (~40%) of whole body mass while enabling body movement, including physical work and exercise. At the core of this system is the neuromuscular junction (NMJ) which is the vital synapse transducing electrical impulses from the [...] Read more.
The neuromuscular system accounts for a large portion (~40%) of whole body mass while enabling body movement, including physical work and exercise. At the core of this system is the neuromuscular junction (NMJ) which is the vital synapse transducing electrical impulses from the motor neurons to their post-synaptic myofibers. Recent findings suggest that subcellular features (active zones) of the NMJ are distinctly sensitive to changes in activity relative to cellular features (nerve terminal branches, vesicles, receptors) of the NMJ. In the present investigation, muscles with different recruitment patterns, functions, and myofiber type profiles (soleus, plantaris, extensor digitorum longus [EDL]) were studied to quantify both cellular and subcellular NMJ characteristics along with myofiber type profiles. Results indicated that, in general, dimensions of subcellular components of NMJs mirrored cellular NMJ features when examining inter-muscle NMJ architecture. Typically, it was noted that the NMJs of the soleus, with its most pronounced recruitment pattern, were larger (p < 0.05) than NMJs of less recruited muscles. Moreover, it was revealed that myofiber size did not dictate NMJ size as soleus muscles displayed the smallest fibers (p < 0.05) while the plantaris muscles exhibited the largest fibers. In total, these data show that activity determines the size of NMJs and that generally, size dimensions of cellular and subcellular components of the NMJ are matched, and that the size of NMJs and their underlying myofibers are uncoupled. Full article
(This article belongs to the Special Issue Cellular Plasticity of the Neuromuscular System)
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22 pages, 3991 KiB  
Article
Skeletal Muscle DNA Methylation and mRNA Responses to a Bout of Higher versus Lower Load Resistance Exercise in Previously Trained Men
by Casey L. Sexton, Joshua S. Godwin, Mason C. McIntosh, Bradley A. Ruple, Shelby C. Osburn, Blake R. Hollingsworth, Nicholas J. Kontos, Philip J. Agostinelli, Andreas N. Kavazis, Tim N. Ziegenfuss, Hector L. Lopez, Ryan Smith, Kaelin C. Young, Varun B. Dwaraka, Andrew D. Frugé, Christopher B. Mobley, Adam P. Sharples and Michael D. Roberts
Cells 2023, 12(2), 263; https://doi.org/10.3390/cells12020263 - 09 Jan 2023
Cited by 10 | Viewed by 3289
Abstract
We sought to determine the skeletal muscle genome-wide DNA methylation and mRNA responses to one bout of lower load (LL) versus higher load (HL) resistance exercise. Trained college-aged males (n = 11, 23 ± 4 years old, 4 ± 3 years self-reported [...] Read more.
We sought to determine the skeletal muscle genome-wide DNA methylation and mRNA responses to one bout of lower load (LL) versus higher load (HL) resistance exercise. Trained college-aged males (n = 11, 23 ± 4 years old, 4 ± 3 years self-reported training) performed LL or HL bouts to failure separated by one week. The HL bout (i.e., 80 Fail) consisted of four sets of back squats and four sets of leg extensions to failure using 80% of participants estimated one-repetition maximum (i.e., est. 1-RM). The LL bout (i.e., 30 Fail) implemented the same paradigm with 30% of est. 1-RM. Vastus lateralis muscle biopsies were collected before, 3 h, and 6 h after each bout. Muscle DNA and RNA were batch-isolated and analyzed using the 850k Illumina MethylationEPIC array and Clariom S mRNA microarray, respectively. Performed repetitions were significantly greater during the 30 Fail versus 80 Fail (p < 0.001), although total training volume (sets × reps × load) was not significantly different between bouts (p = 0.571). Regardless of bout, more CpG site methylation changes were observed at 3 h versus 6 h post exercise (239,951 versus 12,419, respectively; p < 0.01), and nuclear global ten-eleven translocation (TET) activity, but not global DNA methyltransferase activity, increased 3 h and 6 h following exercise regardless of bout. The percentage of genes significantly altered at the mRNA level that demonstrated opposite DNA methylation patterns was greater 3 h versus 6 h following exercise (~75% versus ~15%, respectively). Moreover, high percentages of genes that were up- or downregulated 6 h following exercise also demonstrated significantly inversed DNA methylation patterns across one or more CpG sites 3 h following exercise (65% and 82%, respectively). While 30 Fail decreased DNA methylation across various promoter regions versus 80 Fail, transcriptome-wide mRNA and bioinformatics indicated that gene expression signatures were largely similar between bouts. Bioinformatics overlay of DNA methylation and mRNA expression data indicated that genes related to “Focal adhesion,” “MAPK signaling,” and “PI3K-Akt signaling” were significantly affected at the 3 h and 6 h time points, and again this was regardless of bout. In conclusion, extensive molecular profiling suggests that post-exercise alterations in the skeletal muscle DNA methylome and mRNA transcriptome elicited by LL and HL training bouts to failure are largely similar, and this could be related to equal volumes performed between bouts. Full article
(This article belongs to the Special Issue Cellular Plasticity of the Neuromuscular System)
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Review

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18 pages, 866 KiB  
Review
Current Nutritional and Pharmacological Approaches for Attenuating Sarcopenia
by Kunihiro Sakuma, Kento Hamada, Akihiko Yamaguchi and Wataru Aoi
Cells 2023, 12(19), 2422; https://doi.org/10.3390/cells12192422 - 09 Oct 2023
Cited by 1 | Viewed by 2030
Abstract
Sarcopenia is characterized by a gradual slowing of movement due to loss of muscle mass and quality, decreased power and strength, increased risk of injury from falls, and often weakness. This review will focus on recent research trends in nutritional and pharmacological approaches [...] Read more.
Sarcopenia is characterized by a gradual slowing of movement due to loss of muscle mass and quality, decreased power and strength, increased risk of injury from falls, and often weakness. This review will focus on recent research trends in nutritional and pharmacological approaches to controlling sarcopenia. Because nutritional studies in humans are fairly limited, this paper includes many results from nutritional studies in mammals. The combination of resistance training with supplements containing amino acids is the gold standard for preventing sarcopenia. Amino acid (HMB) supplementation alone has no significant effect on muscle strength or muscle mass in sarcopenia, but the combination of HMB and exercise (whole body vibration stimulation) is likely to be effective. Tea catechins, soy isoflavones, and ursolic acid are interesting candidates for reducing sarcopenia, but both more detailed basic research on this treatment and clinical studies in humans are needed. Vitamin D supplementation has been shown not to improve sarcopenia in elderly individuals who are not vitamin D-deficient. Myostatin inhibitory drugs have been tried in many neuromuscular diseases, but increases in muscle mass and strength are less likely to be expected. Validation of myostatin inhibitory antibodies in patients with sarcopenia has been positive, but excessive expectations are not warranted. Full article
(This article belongs to the Special Issue Cellular Plasticity of the Neuromuscular System)
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17 pages, 574 KiB  
Review
Neuronal Plasticity and Age-Related Functional Decline in the Motor Cortex
by Ritsuko Inoue and Hiroshi Nishimune
Cells 2023, 12(17), 2142; https://doi.org/10.3390/cells12172142 - 25 Aug 2023
Cited by 1 | Viewed by 1637
Abstract
Physiological aging causes a decline of motor function due to impairment of motor cortex function, losses of motor neurons and neuromuscular junctions, sarcopenia, and frailty. There is increasing evidence suggesting that the changes in motor function start earlier in the middle-aged stage. The [...] Read more.
Physiological aging causes a decline of motor function due to impairment of motor cortex function, losses of motor neurons and neuromuscular junctions, sarcopenia, and frailty. There is increasing evidence suggesting that the changes in motor function start earlier in the middle-aged stage. The mechanism underlining the middle-aged decline in motor function seems to relate to the central nervous system rather than the peripheral neuromuscular system. The motor cortex is one of the responsible central nervous systems for coordinating and learning motor functions. The neuronal circuits in the motor cortex show plasticity in response to motor learning, including LTP. This motor cortex plasticity seems important for the intervention method mechanisms that revert the age-related decline of motor function. This review will focus on recent findings on the role of plasticity in the motor cortex for motor function and age-related changes. The review will also introduce our recent identification of an age-related decline of neuronal activity in the primary motor cortex of middle-aged mice using electrophysiological recordings of brain slices. Full article
(This article belongs to the Special Issue Cellular Plasticity of the Neuromuscular System)
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