A data-driven analysis of fiber type architecture over the entire muscle

2020 ◽  
Author(s):  
Davide Bindellini ◽  
Lenard M. Voortman ◽  
Cyriel S. Olie ◽  
Maaike van Putten ◽  
Erik van den Akker ◽  
...  
Keyword(s):  
Cross Sections ◽  
Muscle Function ◽  
Neuromuscular Junctions ◽  
Fiber Type ◽  
Data Driven ◽  
Geometric Features ◽  
Skeletal Muscle Function ◽  
Myhc Isoforms ◽  
Median Region ◽  
Local Sampling

Abstract Background Skeletal muscle function is inferred from the spatial arrangement of muscle fibers architecture, which corresponds to myofiber molecular and metabolic features. Myofiber types can be distinguished by the expression of myosin heavy chain (MyHC) isoforms, representing contraction properties. In most studies, myofiber typing is determined from a local sampling, typically obtained from the muscle median region. This median region is assumed to represent the entire muscle. However, it remains largely unknown to what extent this local sampling represents the entire muscle. Methods We present here a pipeline to study the architecture of muscle fiber type over the entire muscle, from sectioning, staining, imaging to image quantification and data-driven analysis. Results We reconstructed muscle architecture from consecutive cross-sections stained for laminin and MyHC isoforms. Examining the entire muscle using consecutive cross-sections is extremely laborious, we provide consideration to reduce dataset and yet to cover the entire muscle. Analyses of over 15,000 myofibers, showed spatial variations in myofiber geometric features, myofiber type and the distribution of neuromuscular junctions along the entire muscle. Conclusions We suggest that asymmetric spatial distribution of myofiber types, geometric features of myofibers and the neuromuscular junctions along the muscle could affect muscle function. Therefore, instead of a single sampling from a median region, representative regions covering the entire muscle should be investigated in future studies.

scholarly journals Asymmetrical myofiber architecture along the murine tibialis anterior suggests distinct functional regions

2020 ◽  
Author(s):  
Davide Bindellini ◽  
Lenard M. Voortman ◽  
Cyriel S. Olie ◽  
Maaike van Putten ◽  
Erik van den Akker ◽  
...  
Keyword(s):  
Cross Sections ◽  
Tibialis Anterior ◽  
Neuromuscular Junctions ◽  
Tibialis Anterior Muscle ◽  
Wild Type Mouse ◽  
Spatial Arrangement ◽  
Skeletal Muscle Function ◽  
Functional Regions ◽  
Myhc Isoforms ◽  
Local Sampling

AbstractSkeletal muscle function is inferred from the spatial arrangement of myofiber architecture and the molecular and metabolic features of myofibers. Features of myofiber types can be distinguished by the expression of myosin heavy chain (MyHC) isoforms, indicating contraction properties. In most studies, a local sampling, typically obtained from the median part of the muscle, is used to represent the whole muscle. It remains largely unknown to what extent this local sampling represents the entire muscle. Here we studied myofiber architecture over the entire wild type mouse tibialis anterior muscle, using a high-throughput procedure combining automatic imaging and image processing analyses. We reconstructed myofiber architecture from consecutive cross-sections stained for laminin and MyHC isoforms. The data showed a marked variation in myofiber geometric features, as well as MyHC expression and the distribution of neuromuscular junctions, and suggest that muscle regions with distinct properties can be defined along the entire muscle. We show that in these muscle regions myofiber geometric properties align with biological function and propose that future studies on muscle alterations in pathological or physiological conditions should consider the entire muscle.

Development of soleus muscles in SHR: relationship of muscle deficits to rise in blood pressure

1994 ◽  
Vol 267 (3) ◽  
pp. C827-C835 ◽  
Author(s):  
A. Atrakchi ◽  
S. D. Gray ◽  
R. C. Carlsen
Keyword(s):  
Blood Pressure ◽  
Muscle Function ◽  
Skeletal Muscles ◽  
Fiber Type ◽  
Hypertensive Rats ◽  
Skeletal Muscle Function ◽  
Spontaneously Hypertensive ◽  
Age Related ◽  
Wistar Kyoto ◽  
Relationship Of

Skeletal muscles from 24- to 28-wk-old spontaneously hypertensive rats (SHR) exhibit decreased contractile capacity and resistance to fatigue. The present study was designed to determine the age at which these deficits first appear and their relationship to the development and progression of the rise in blood pressure. SHR soleus was significantly weaker than age-matched Wistar-Kyoto (WKY) soleus at all ages studied, but resistance to fatigue varied with age. Soleus muscles in 6- to 8-wk-old SHR were, on average, more fatigue resistant than age-matched WKY muscles. Fatigue resistance in 16- to 18-wk-old animals, however, was similar in the two strains. There were no significant differences in soleus growth or fiber type distributions in the strains between 6 and 18 wk of age. WKY soleus in 24- to 28-wk-old animals were hyperpolarized after the fatigue test. SHR fibers, in contrast, did not hyperpolarize after exercise, possibly reflecting an age-related reduction in sarcolemmal Na+ pump number or function. Soleus in younger SHR also provided an indication of a developing membrane dysfunction, since extracellularly recorded M waves showed greater changes in SHR than in age-matched WKY muscles during exercise. The rise of blood pressure in SHR is genetically based, but it is not clear that the genetic defects responsible for hypertension also produce the observed deficits in skeletal muscle function.

scholarly journals Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice

2021 ◽  
Author(s):  
Priya Balasubramanian ◽  
Anne E Schaar ◽  
Grace E Gustafson ◽  
Alex B Smith ◽  
Porsha R Howell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Receptor Agonist ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Fiber Type ◽  
Adiponectin Receptor ◽  
Mitochondrial Activity ◽  
Skeletal Muscle Function ◽  
Aged Mice

The loss of skeletal muscle function with age, known as sarcopenia, significantly reduces independence and quality of life and can have significant metabolic consequences. Although exercise is effective in treating sarcopenia it is not always a viable option clinically, and currently there are no pharmacological therapeutic interventions for sarcopenia. Here we show that chronic treatment with pan-adiponectin receptor agonist AdipoRon improved muscle function in male mice by a mechanism linked to skeletal muscle metabolism and tissue remodeling. In aged mice, 6 weeks of AdipoRon treatment improved skeletal muscle functional measures in vivo and ex vivo. Improvements were linked to changes in fiber type, including an enrichment of oxidative fibers, and an increase in mitochondrial activity. In young mice, 6 weeks of AdipoRon treatment improved contractile force and activated the energy sensing kinase AMPK and the mitochondrial regulator PGC-1a (peroxisome proliferator activated receptor gamma coactivator 1 alpha). In cultured cells, the AdipoRon induced stimulation of AMPK and PGC-1a was associated with increased mitochondrial membrane potential, reorganization of mitochondrial architecture, increased respiration, and increased ATP production. Furthermore, the ability of AdipoRon to stimulate AMPK and PGC1a was conserved in nonhuman primate cultured cells. These data show that AdipoRon is an effective agent for the prevention of sarcopenia in mice and indicate that its effects translate to primates, suggesting it may also be a suitable therapeutic for sarcopenia in clinical application.

scholarly journals High-throughput data-driven analysis of myofiber composition reveals muscle-specific disease and age-associated patterns

2018 ◽  
Author(s):  
Vered Raz ◽  
Yotam Raz ◽  
Davy van de Vijver ◽  
Davide Bindellini ◽  
Maaike van Putten ◽  
...  
Keyword(s):  
High Throughput ◽  
Muscle Function ◽  
Age Groups ◽  
Data Driven ◽  
Muscle Type ◽  
Muscle Involvement ◽  
High Throughput Data ◽  
Myhc Isoforms ◽  
Visual Assessments ◽  
Two Age Groups

Contractile properties of myofibers are dictated by the abundance of myosin heavy chain (MyHC) isoforms. MyHC composition designates muscle function and its alterations could unravel differential muscle involvement in muscular dystrophies and aging. Current analyses are limited to visual assessments in which myofibers expressing multiple MyHC isoforms are prone to misclassifications. As a result, complex patterns and subtle alterations are unidentified. We developed a high-throughput data-driven myofiber analysis to quantitatively describe the variations in myofibers across the muscle. We investigated alterations in myofiber composition between genotypes, two muscles and two age groups. We show that this analysis facilitates the discovery of complex myofiber compositions and its dependency on age, muscle type and genetic conditions.

Lower limb skeletal muscle function after 6 wk of bed rest

1997 ◽  
Vol 82 (1) ◽  
pp. 182-188 ◽  
Author(s):  
H. E. Berg ◽  
L. Larsson ◽  
P. A. Tesch
Keyword(s):  
Skeletal Muscle ◽  
Lower Limb ◽  
Muscle Function ◽  
Fiber Type ◽  
Vastus Lateralis ◽  
Knee Extensor ◽  
Bed Rest ◽  
Emg Activity ◽  
Type I ◽  
Skeletal Muscle Function

Berg, H. E., L. Larsson, and P. A. Tesch. Lower limb skeletal muscle function after 6 wk of bed rest. J. Appl. Physiol. 82(1): 182–188, 1997.—Force, electromyographic (EMG) activity, muscle mass, and fiber characteristics were studied in seven healthy men before and after 6 wk of bed rest. Maximum voluntary isometric and concentric knee extensor torque decreased ( P < 0.05) uniformly across angular velocities by 25–30% after bed rest. Maximum quadricep rectified EMG decreased by 19 ± 23%, whereas submaximum (100-Nm isometric action) EMG increased by 44 ± 28%. Knee extensor muscle cross-sectional area (CSA), assessed by using magnetic resonance imaging, decreased by 14 ± 4%. Maximum torque per knee extensor CSA decreased by 13 ± 9%. Vastus lateralis fiber CSA decreased 18 ± 14%. Neither type I, IIA, and IIB fiber percentages nor their relative proportions of myosin heavy chain (MHC) isoforms were altered after bed rest. Because the decline in strength could not be entirely accounted for by decreased muscle CSA, it is suggested that the strength loss is also due to factors resulting in decreased neural input to muscle and/or reduced specific tension of muscle, as evidenced by a decreased torque/EMG ratio. Additionally, it is concluded that muscle unloading in humans does not induce important changes in fiber type or MHC composition or in vivo muscle contractile properties.

scholarly journals Gait disturbances and muscle dysfunction in fibroblast growth factor 2 knockout mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. Homer-Bouthiette ◽  
L. Xiao ◽  
Marja M. Hurley
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Strength ◽  
Fibroblast Growth Factor ◽  
Muscle Function ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Skeletal Muscle Function ◽  
Age Related ◽  
Gait Disturbances

AbstractFibroblast growth factor 2 (FGF2) is important in musculoskeletal homeostasis, therefore the impact of reduction or Fgf2 knockout on skeletal muscle function and phenotype was determined. Gait analysis as well as muscle strength testing in young and old WT and Fgf2KO demonstrated age-related gait disturbances and reduction in muscle strength that were exacerbated in the KO condition. Fgf2 mRNA and protein were significantly decreased in skeletal muscle of old WT compared with young WT. Muscle fiber cross-sectional area was significantly reduced with increased fibrosis and inflammatory infiltrates in old WT and Fgf2KO vs. young WT. Inflammatory cells were further significantly increased in old Fgf2KO compared with old WT. Lipid-related genes and intramuscular fat was increased in old WT and old Fgf2KO with a further increase in fibro-adipocytes in old Fgf2KO compared with old WT. Impaired FGF signaling including Increased β-Klotho, Fgf21 mRNA, FGF21 protein, phosphorylated FGF receptors 1 and 3, was observed in old WT and old Fgf2KO. MAPK/ ERK1/2 was significantly increased in young and old Fgf2KO. We conclude that Fgf2KO, age-related decreased FGF2 in WT mice, and increased FGF21 in the setting of impaired Fgf2 expression likely contribute to impaired skeletal muscle function and sarcopenia in mice.

scholarly journals Fourteen days of smoking cessation improves muscle fatigue resistance and reverses markers of systemic inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Z. Darabseh ◽  
Thomas M. Maden-Wilkinson ◽  
George Welbourne ◽  
Rob C. I. Wüst ◽  
Nessar Ahmed ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Smoking Cessation ◽  
Muscle Fatigue ◽  
Fatigue Resistance ◽  
Systemic Inflammation ◽  
Muscle Function ◽  
Low Grade ◽  
Skeletal Muscle Function ◽  
Tnf Α

AbstractCigarette smoking has a negative effect on respiratory and skeletal muscle function and is a risk factor for various chronic diseases. To assess the effects of 14 days of smoking cessation on respiratory and skeletal muscle function, markers of inflammation and oxidative stress in humans. Spirometry, skeletal muscle function, circulating carboxyhaemoglobin levels, advanced glycation end products (AGEs), markers of oxidative stress and serum cytokines were measured in 38 non-smokers, and in 48 cigarette smokers at baseline and after 14 days of smoking cessation. Peak expiratory flow (p = 0.004) and forced expiratory volume in 1 s/forced vital capacity (p = 0.037) were lower in smokers compared to non-smokers but did not change significantly after smoking cessation. Smoking cessation increased skeletal muscle fatigue resistance (p < 0.001). Haemoglobin content, haematocrit, carboxyhaemoglobin, total AGEs, malondialdehyde, TNF-α, IL-2, IL-4, IL-6 and IL-10 (p < 0.05) levels were higher, and total antioxidant status (TAS), IL-12p70 and eosinophil numbers were lower (p < 0.05) in smokers. IL-4, IL-6, IL-10 and IL-12p70 had returned towards levels seen in non-smokers after 14 days smoking cessation (p < 0.05), and IL-2 and TNF-α showed a similar pattern but had not yet fully returned to levels seen in non-smokers. Haemoglobin, haematocrit, eosinophil count, AGEs, MDA and TAS did not significantly change with smoking cessation. Two weeks of smoking cessation was accompanied with an improved muscle fatigue resistance and a reduction in low-grade systemic inflammation in smokers.

The KATP channel Kir6.2 subunit content is higher in glycolytic than oxidative skeletal muscle fibers

2011 ◽  
Vol 301 (4) ◽  
pp. R916-R925 ◽  
Author(s):  
Krystyna Banas ◽  
Charlene Clow ◽  
Bernard J. Jasmin ◽  
Jean-Marc Renaud
Keyword(s):  
Skeletal Muscle ◽  
Cross Sections ◽  
Fiber Type ◽  
Energy Levels ◽  
Muscle Fibers ◽  
Metabolic Stress ◽  
Oxidative Capacity ◽  
Fiber Types ◽  
Fiber Damage ◽  
The Individual

It has long been suggested that in skeletal muscle, the ATP-sensitive K+ channel (KATP) channel is important in protecting energy levels and that abolishing its activity causes fiber damage and severely impairs function. The responses to a lack of KATP channel activity vary between muscles and fibers, with the severity of the impairment being the highest in the most glycolytic muscle fibers. Furthermore, glycolytic muscle fibers are also expected to face metabolic stress more often than oxidative ones. The objective of this study was to determine whether the t-tubular KATP channel content differs between muscles and fiber types. KATP channel content was estimated using a semiquantitative immunofluorescence approach by staining cross sections from soleus, extensor digitorum longus (EDL), and flexor digitorum brevis (FDB) muscles with anti-Kir6.2 antibody. Fiber types were determined using serial cross sections stained with specific antimyosin I, IIA, IIB, and IIX antibodies. Changes in Kir6.2 content were compared with changes in CaV1.1 content, as this Ca2+ channel is responsible for triggering Ca2+ release from sarcoplasmic reticulum. The Kir6.2 content was the lowest in the oxidative soleus and the highest in the glycolytic EDL and FDB. At the individual fiber level, the Kir6.2 content within a muscle was in the order of type IIB > IIX > IIA ≥ I. Interestingly, the Kir6.2 content for a given fiber type was significantly different between soleus, EDL, and FDB, and highest in FDB. Correlations of relative fluorescence intensities from the Kir6.2 and CaV1.1 antibodies were significant for all three muscles. However, the variability in content between the three muscles or individual fibers was much greater for Kir6.2 than for CaV1.1. It is suggested that the t-tubular KATP channel content increases as the glycolytic capacity increases and as the oxidative capacity decreases and that the expression of KATP channels may be linked to how often muscles/fibers face metabolic stress.

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