Changes In Fiber Type Composition Research Articles

No ageing-related increase in fibre type grouping in sprint-trained masters runners: A 10-year follow-up study.

Previous research suggests that an ageing-associated remodelling and loss of motor units due to motor neuron death contributes significantly to muscle weakness in old age. In histological sections, motor unit remodelling is reflected by increased fibre type grouping. While regular exercise may not attenuate the loss of motor units during ageing, it has been suggested to facilitate reinnervation resulting in larger motor units, and a higher number and larger fibre type groups in histological sections of muscles from aged individuals. In a 10-year follow-up study, we assessed changes in the prevalence and size of fibre type groups in the vastus lateralis muscle from 34 male masters sprinters (40-85years at start). Over the 10years, there was an ageing-related reduction in performance in the 60-m sprint (P<0.001) without significant changes in fibre type composition and fibre cross-sectional area. Neither the number of fibre type groups, defined as a fibre surrounded exclusively by fibres of the same type, nor the group size changed significantly in the 10-year period. These histological data show that there is limited to no significant fibre type grouping over a 10-year period in masters athletes who continued sprint run training. This observation challenges the paradigm that ageing, at least in systematically trained sprinters, is associated with motor unit remodelling.

Effects of a 10-d Military Field Exercise on Body Composition, Physical Performance, and Muscle Cells in Men and Women.

This study aimed to investigate the effects of a demanding military field exercise on physical performance, body composition, and muscle cellular outcomes in men and women. Ten men (20.5 ± 0.5 yr) and 8 women (21.4 ± 1.4 yr) completed a 10-d field exercise consisting of extensive physical activity with food and sleep restriction. Acquisition of body composition, physical performance, blood, and muscle biopsies samples were done before and 1, 7, and 14 d after the exercise. There were no sex differences in the response to the exercise. Body mass was decreased with 5.6% ± 1.8% and fat mass with 31% ± 11% during the exercise. Both were still reduced after 14 d (2.5% ± 2.3%, P < 0.001, and 12.5% ± 7.7%, P < 0.001, respectively). Isometric leg strength did not change. Peak leg extension torque at 240°·s -1 and counter movement jump height were reduced with 4.6% ± 4.8% ( P = 0.012) and 6.7% ± 6.2% ( P < 0.001), respectively, and was still reduced after 14 d (4.3% ± 4.2%, P = 0.002, and 4.1% ± 4.7%, P = 0.030). No changes occurred in fiber CSA, fiber types, proteins involved in calcium handling, or HSP70. During the exercise, αB-crystallin levels decreased by 14% ± 19% ( P = 0.024) in the cytosolic fraction and staining intensity on muscle sections tended to increase (17% ± 25%, P = 0.076). MuRF1 levels in the cytosolic fraction tended to decrease (19% ± 35%) and increased with 85% ± 105% ( P = 0.003) in the cytoskeletal fraction 1 wk after the exercise. The field exercise resulted in reduced body mass and physical performance in both sexes. The ability to produce force at high contraction velocities and explosive strength was more affected than isometric strength, but this was not related to any changes in fiber type composition, fiber area, Ca 2+ handling, or fiber type-specific muscle damage.

Thyroid hormone receptor α in skeletal muscle is essential for T3-mediated increase in energy expenditure.

Thyroid hormones are important for homeostatic control of energy metabolism and body temperature. Although skeletal muscle is considered a key site for thyroid action, the contribution of thyroid hormone receptor signaling in muscle to whole‐body energy metabolism and body temperature has not been resolved. Here, we show that T3‐induced increase in energy expenditure requires thyroid hormone receptor alpha 1 (TRα1) in skeletal muscle, but that T3‐mediated elevation in body temperature is achieved in the absence of muscle‐TRα1. In slow‐twitch soleus muscle, loss‐of‐function of TRα1 (TRαHSACre) alters the fiber‐type composition toward a more oxidative phenotype. The change in fiber‐type composition, however, does not influence the running capacity or motivation to run. RNA‐sequencing of soleus muscle from WT mice and TRαHSACre mice revealed differentiated transcriptional regulation of genes associated with muscle thermogenesis, such as sarcolipin and UCP3, providing molecular clues pertaining to the mechanistic underpinnings of TRα1‐linked control of whole‐body metabolic rate. Together, this work establishes a fundamental role for skeletal muscle in T3‐stimulated increase in whole‐body energy expenditure.

Motoneuron deafferentation and gliosis occur in association with neuromuscular regressive changes during ageing in mice.

BackgroundThe cellular mechanisms underlying the age‐associated loss of muscle mass and function (sarcopenia) are poorly understood, hampering the development of effective treatment strategies. Here, we performed a detailed characterization of age‐related pathophysiological changes in the mouse neuromuscular system.MethodsYoung, adult, middle‐aged, and old (1, 4, 14, and 24–30 months old, respectively) C57BL/6J mice were used. Motor behavioural and electrophysiological tests and histological and immunocytochemical procedures were carried out to simultaneously analyse structural, molecular, and functional age‐related changes in distinct cellular components of the neuromuscular system.ResultsAgeing was not accompanied by a significant loss of spinal motoneurons (MNs), although a proportion (~15%) of them in old mice exhibited an abnormally dark appearance. Dark MNs were also observed in adult (~9%) and young (~4%) animals, suggesting that during ageing, some MNs undergo early deleterious changes, which may not lead to MN death. Old MNs were depleted of cholinergic and glutamatergic inputs (~40% and ~45%, respectively, P < 0.01), suggestive of age‐associated alterations in MN excitability. Prominent microgliosis and astrogliosis [~93% (P < 0.001) and ~100% (P < 0.0001) increase vs. adults, respectively] were found in old spinal cords, with increased density of pro‐inflammatory M1 microglia and A1 astroglia (25‐fold and 4‐fold increase, respectively, P < 0.0001). Ageing resulted in significant reductions in the nerve conduction velocity and the compound muscle action potential amplitude (~30%, P < 0.05, vs. adults) in old distal plantar muscles. Compared with adult muscles, old muscles exhibited significantly higher numbers of both denervated and polyinnervated neuromuscular junctions, changes in fibre type composition, higher proportion of fibres showing central nuclei and lipofuscin aggregates, depletion of satellite cells, and augmented expression of different molecules related to development, plasticity, and maintenance of neuromuscular junctions, including calcitonin gene‐related peptide, growth associated protein 43, agrin, fibroblast growth factor binding protein 1, and transforming growth factor‐β1. Overall, these alterations occurred at varying degrees in all the muscles analysed, with no correlation between the age‐related changes observed and myofiber type composition or muscle topography.ConclusionsOur data provide a global view of age‐associated neuromuscular changes in a mouse model of ageing and help to advance understanding of contributing pathways leading to development of sarcopenia.

Skeletal Muscle Fiber Type in Hypoxia: Adaptation to High-Altitude Exposure and Under Conditions of Pathological Hypoxia.

Skeletal muscle is able to modify its size, and its metabolic/contractile properties in response to a variety of stimuli, such as mechanical stress, neuronal activity, metabolic and hormonal influences, and environmental factors. A reduced oxygen availability, called hypoxia, has been proposed to induce metabolic adaptations and loss of mass in skeletal muscle. In addition, several evidences indicate that muscle fiber-type composition could be affected by hypoxia. The main purpose of this review is to explore the adaptation of skeletal muscle fiber-type composition to exposure to high altitude (ambient hypoxia) and under conditions of pathological hypoxia, including chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and obstructive sleep apnea syndrome (OSAS). The muscle fiber-type composition of both adult animals and humans is not markedly altered during chronic exposure to high altitude. However, the fast-to-slow fiber-type transition observed in hind limb muscles during post-natal development is impaired in growing rats exposed to severe altitude. A slow-to-fast transition in fiber type is commonly found in lower limb muscles from patients with COPD and CHF, whereas a transition toward a slower fiber-type profile is often found in the diaphragm muscle in these two pathologies. A slow-to-fast transformation in fiber type is generally observed in the upper airway muscles in rodent models of OSAS. The factors potentially responsible for the adaptation of fiber type under these hypoxic conditions are also discussed in this review. The impaired locomotor activity most likely explains the changes in fiber type composition in growing rats exposed to severe altitude. Furthermore, chronic inactivity and muscle deconditioning could result in the slow-to-fast fiber-type conversion in lower limb muscles during COPD and CHF, while the factors responsible for the adaptation of muscle fiber type during OSAS remain hypothetical. Finally, the role played by cellular hypoxia, hypoxia-inducible factor-1 alpha (HIF-1α), and other molecular regulators in the adaptation of muscle fiber-type composition is described in response to high altitude exposure and conditions of pathological hypoxia.

Modelling performance and skeletal muscle adaptations with exponential growth functions during resistance training

ABSTRACTSystem theory is classically applied to describe and to predict the effects of training load on performance. The classic models are structured by impulse-type transfer functions, nevertheless, most biological adaptations display exponential growth kinetics. The aim of this study was to propose an extension of the model structure taking into account the exponential nature of skeletal muscle adaptations by using a genetic algorithm. Thus, the conventional impulse-type model was applied in 15 resistance trained rodents and compared with exponential growth-type models. Even if we obtained a significant correlation between actual and modelled performances for all the models, our data indicated that an exponential model is associated with more suitable parameters values, especially the time constants that correspond to the positive response to training. Moreover, positive adaptations predicted with an exponential component showed a strong correlation with the main structural adaptations examined in skeletal muscles, i.e. hypertrophy (R2 = 0.87, 0.96 and 0.99, for type 1, 2A and 2X cross-sectional area fibers, respectively) and changes in fiber-type composition (R2 = 0.81 and 0.79, for type 1 and 2A fibers, respectively). Thus, an exponential model succeeds to describe both performance variations with relevant time constants and physiological adaptations that take place during resistance training.

Effect of Chronic Alcohol Abuse on Anabolic and Catabolic Signaling Pathways in Human Skeletal Muscle.

Animal studies showed that alcoholic myopathy is characterized by the reduction in myofiber cross-sectional area (CSA) and by impaired anabolic signaling. The goal of this study was to compare changes in CSA and fiber type composition with modifications in anabolic and catabolic signaling pathways at the early stages of alcohol misuse in humans. Skeletal muscle samples from 7 male patients with chronic alcohol abuse (AL; 47.7±2.0years old; alcohol misuse duration 7.7±0.6years) were compared with muscle from a control group of 7 healthy men (C; 39.7±5.0years old). Biopsies from vastus lateralis muscles were taken and analyzed for the changes in fiber type composition, fiber CSA, and for the alterations in anabolic and catabolic signaling pathways. AL patients did not have detectable clinical myopathy symptoms or muscle fiber atrophy, but the relative proportion of fast fibers was increased. There was a significant decrease in IGF-1 in plasma and IRS-1 protein content in muscle of AL group. Levels of total and phosphorylated p70S6K1, GSK3β, and p90RSK1 were not different between AL and C groups. Muscle of AL patients had increased mRNA expression of HSP70 and HSP90. A marker of anabolic pathway p-4E-BP1 was decreased, while catabolic markers (MuRF-1, MAFbx, ubiquitinated proteins) were increased in AL patients when compared with C group. At the early stages of alcohol misuse in humans, changes in the regulation of anabolic and catabolic signaling pathways precede the development of skeletal muscle atrophy and manifestation of clinical symptoms of alcoholic myopathy.

Tensiomyographic Assessment of Muscle Contractile Properties in 9- to 14-Year Old Children.

While there are numerous data on the skeletal muscle fiber type composition in adults, little is known about the changes in fiber type composition and contractile properties during maturational growth in children. Using noninvasive tensiomyography, we measured contraction time (Tc), an indirect estimate of the myosin heavy chain I (MHC-I) proportion, to assess the longitudinal changes of the biceps brachii (BB), biceps femois (BF), vastus lateralis (VL), and erector spinae (ES) muscles in 53 boys and 54 girls. The children were 9 years at the start of the study and returned for 5 follow-up measurements until the age of 14 years. The ES has the shortest and the BF has the longest Tc. The VL and ES of boys have shorter Tc than those of girls. When applying the relationship between proportion of MHC-I and Tc established in adults to children's TMG data, we found a slow-to-fast transition in the VL between, at least, the ages of 6 to 10 years, when it stabilized to adult proportions. Regular participation in sports was associated with a faster BF, but not in the VL. Our data represents a first non-invasive indication of the developmental changes in muscle fiber type composition in children.

Perm1 enhances mitochondrial biogenesis, oxidative capacity, and fatigue resistance in adult skeletal muscle.

Skeletal muscle mitochondrial content and oxidative capacity are important determinants of muscle function and whole-body health. Mitochondrial content and function are enhanced by endurance exercise and impaired in states or diseases where muscle function is compromised, such as myopathies, muscular dystrophies, neuromuscular diseases, and age-related muscle atrophy. Hence, elucidating the mechanisms that control muscle mitochondrial content and oxidative function can provide new insights into states and diseases that affect muscle health. In past studies, we identified Perm1 (PPARGC1- and ESRR-induced regulator, muscle 1) as a gene induced by endurance exercise in skeletal muscle, and regulating mitochondrial oxidative function in cultured myotubes. The capacity of Perm1 to regulate muscle mitochondrial content and function in vivo is not yet known. In this study, we use adeno-associated viral (AAV) vectors to increase Perm1 expression in skeletal muscles of 4-wk-old mice. Compared to control vector, AAV1-Perm1 leads to significant increases in mitochondrial content and oxidative capacity (by 40-80%). Moreover, AAV1-Perm1-transduced muscles show increased capillary density and resistance to fatigue (by 33 and 31%, respectively), without prominent changes in fiber-type composition. These findings suggest that Perm1 selectively regulates mitochondrial biogenesis and oxidative function, and implicate Perm1 in muscle adaptations that also occur in response to endurance exercise.

Muscle-derived extracellular signal-regulated kinases 1 and 2 are required for the maintenance of adult myofibers and their neuromuscular junctions.

The Ras-extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway appears to be important for the development, maintenance, aging, and pathology of mammalian skeletal muscle. Yet no gene targeting of Erk1/2 in muscle fibers in vivo has been reported to date. We combined a germ line Erk1 mutation with Cre-loxP Erk2 inactivation in skeletal muscle to produce, for the first time, mice lacking ERK1/2 selectively in skeletal myofibers. Animals lacking muscle ERK1/2 displayed stunted postnatal growth, muscle weakness, and a shorter life span. Their muscles examined in this study, sternomastoid and tibialis anterior, displayed fragmented neuromuscular synapses and a mixture of modest fiber atrophy and loss but failed to show major changes in fiber type composition or absence of cell surface dystrophin. Whereas the lack of only ERK1 had no effects on the phenotypes studied, the lack of myofiber ERK2 explained synaptic fragmentation in the sternomastoid but not the tibialis anterior and a decrease in the expression of the acetylcholine receptor (AChR) epsilon subunit gene mRNA in both muscles. A reduction in AChR protein was documented in line with the above mRNA results. Evidence of partial denervation was found in the sternomastoid but not the tibialis anterior. Thus, myofiber ERK1/2 are differentially required for the maintenance of myofibers and neuromuscular synapses in adult mice.

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Ultrasound-guided biopsy of thecricoarytenoideus lateralismuscle: Technique and safety in horses

Current diagnosis of recurrent laryngeal neuropathy (RLN) depends upon disease recognition in the clinically affected horse. Biopsy of the intrinsic laryngeal muscles may provide a method to identify the changes in fibre-type composition that occur in RLN before clinical signs become apparent. To develop an ultrasound-guided biopsy technique of the left cricoarytenoideus lateralis muscle (CALM) and evaluate its efficacy and safety in vivo. A longitudinal descriptive study. Six standing horses underwent ultrasound-guided biopsy of the left CALM. Frozen muscle cores were obtained with a breast biopsy tool. Serial endoscopic, ultrasonographic and physical examinations before and for 8 weeks after the biopsy were assessed for iatrogenic trauma. Histologies of representative muscle core cross-sections were analysed for the total number of muscle fibres obtained with each biopsy. There were no immediate complications of the procedure and the left CALM was harvested in all instances. Biopsy samples had an average weight of 0.043 g (range = 0.023-0.077 g) and contained 3418 fibres in cross-section (range = 711-7143). Laryngeal endoscopic grade did not change significantly between prebiopsy and the end of the 8 week follow-up. The left CALM had significantly greater echogenicity than the right throughout the study (P<0.001), but there was no difference between the prebiopsy CALM echogenicity and that at completion of the study. Ultrasound-guided biopsy of the left CALM is safe and well tolerated, providing a minimally invasive method to obtain muscle from healthy horses. This new technique may be applicable in research and clinical settings.

Constitutive Expression of Yes-Associated Protein (Yap) in Adult Skeletal Muscle Fibres Induces Muscle Atrophy and Myopathy

The aim of this study was to investigate the function of the Hippo pathway member Yes-associated protein (Yap, gene name Yap1) in skeletal muscle fibres in vivo. Specifically we bred an inducible, skeletal muscle fibre-specific knock-in mouse model (MCK-tTA-hYAP1 S127A) to test whether the over expression of constitutively active Yap (hYAP1 S127A) is sufficient to drive muscle hypertrophy or stimulate changes in fibre type composition. Unexpectedly, after 5–7 weeks of constitutive hYAP1 S127A over expression, mice suddenly and rapidly lost 20–25% body weight and suffered from gait impairments and kyphosis. Skeletal muscles atrophied by 34–40% and the muscle fibre cross sectional area decreased by ≈40% when compared to control mice. Histological analysis revealed evidence of skeletal muscle degeneration and regeneration, necrotic fibres and a NADH-TR staining resembling centronuclear myopathy. In agreement with the histology, mRNA expression of markers of regenerative myogenesis (embryonic myosin heavy chain, Myf5, myogenin, Pax7) and muscle protein degradation (atrogin-1, MuRF1) were significantly elevated in muscles from transgenic mice versus control. No significant changes in fibre type composition were detected using ATPase staining. The phenotype was largely reversible, as a cessation of hYAP1 S127A expression rescued body and muscle weight, restored muscle morphology and prevented further pathological progression. To conclude, high Yap activity in muscle fibres does not induce fibre hypertrophy nor fibre type changes but instead results in a reversible atrophy and deterioration.

Influence of botulinum toxin on rabbit jaw muscle activity and anatomy

Muscles can adapt their fiber properties to accommodate to new conditions. We investigated the extent to which a decrease in muscle activation can cause an adaptation of fiber properties in synergistic and antagonistic jaw muscles. Three months after the injection of botulinum toxin type A in one masseter (anterior or posterior) muscle changes in fiber type composition and fiber cross-sectional areas in jaw muscles were studied at the microscopic level. The injected masseter showed a steep increase in myosin type IIX fibers, whereas fast fibers decreased by about 50% in size. Depending on the injection site, both synergistic and antagonistic muscles showed a significant increase in the size of their fast IIA fibers, sometimes combined with an increased number of IIX fibers. Silencing the activity in the masseter not only causes changes in the fibers of the injected muscle but also leads to changes in other jaw muscles.

What causesin vivomuscle specific tension to increase following resistance training?

It is not known why in vivo muscle specific tension increases following resistance training in humans but changes in muscle fibre-type composition, increased single-fibre specific tension or lateral force transmission might provide explanations. Lateral force transmission would increase specific tension but decrease contraction velocity, thus not affecting maximal power per unit muscle volume. In vivo muscle specific tension, power output and muscle volume were determined in the quadriceps femoris of 42 young men, while myosin heavy chain (MyHC) isoform composition, single-fibre (SF) specific tension, SF maximal shortening velocity (V(max)) and SF peak power (W(max)) of the vastus lateralis were established in a subsample (n = 17) before and after high-intensity leg-extension resistance training (3 sessions week(-1) for 9 weeks). Following training, in vivo muscle specific tension increased by 17% but the power output/muscle volume ratio remained unaltered. Furthermore, there was no relationship between the training-induced decrease in MyHC IIX and the change in specific tension in vivo. In addition, SF specific tension, V(max) and W(max) were unchanged following training. In conclusion, a change in fibre-type composition does not explain the increased in vivo specific tension, nor does it seem likely that increased myofilament packing occurred with resistance training. However, an unchanged in vivo power per unit muscle volume is in accordance with the notion of enhanced lateral force transmission after strength training.

Myostatin knockout mice increase oxidative muscle phenotype as an adaptive response to exercise

Myostatin-deficient mice (MSTN (-/-)) display excessive muscle mass and this is associated with a profound loss of oxidative metabolic properties. In this study we analysed the effect of two endurance-based exercise regimes, either a forced high-impact swim training or moderate intensity voluntary wheel running on the adaptive properties of the tibialis anterior and plantaris muscle from MSTN (-/-) mice. MSTN (-/-) and wild type (MSTN (+/+)) animals had comparable performances in the wheel running regime in terms of distance, average speed and time, but MSTN (-/-) mice showed a reduced ability to sustain a high-impact activity via swimming. Swim training elicited muscle specific adaptations on fibre type distribution in MSTN (-/-); the tibialis anterior displaying a partial transformation in contrast to the plantaris which showed no change. Conversely, wheel running induced similar changes in fibre type composition of both muscles, favouring transitions from IIB-to-IIA. Succinate dehydrogenase activity, an indicator of mitochondrial oxidative potential was increased in response to either exercise regime, with wheel running eliciting more robust changes in the MSTN (-/-) muscles. Examination of the cross sectional area of individual fibre types showed genotype-specific responses with MSTN (-/-) mice exhibiting an incapability of fibre enlargement following the wheel running regime, as opposed to MSTN (+/+) mice and a greater susceptibility to muscle fibre area loss following swimming. In conclusion, the muscle fibre hypertrophy, oxidative capacity and glycolytic phenotype of myostatin deficient muscle can be altered with endurance exercise regimes.

Gain-of-function R225Q Mutation in AMP-activated Protein Kinase γ3 Subunit Increases Mitochondrial Biogenesis in Glycolytic Skeletal Muscle

AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (alpha) and two regulatory subunits (beta and gamma), that works as a cellular energy sensor. The existence of multiple heterotrimeric complexes provides a molecular basis for the multiple roles of this highly conserved signaling system. The AMPK gamma3 subunit is predominantly expressed in skeletal muscle, mostly in type II glycolytic fiber types. We determined whether the AMPK gamma3 subunit has a role in signaling pathways that mediate mitochondrial biogenesis in skeletal muscle. We provide evidence that overexpression or ablation of the AMPK gamma3 subunit does not appear to play a critical role in defining mitochondrial content in resting skeletal muscle. However, overexpression of a mutant form (R225Q) of the AMPK gamma3 subunit (Tg-AMPKgamma3(225Q)) increases mitochondrial biogenesis in glycolytic skeletal muscle. These adaptations are associated with an increase in expression of the co-activator PGC-1alpha and several transcription factors that regulate mitochondrial biogenesis, including NRF-1, NRF-2, and TFAM. Succinate dehydrogenase staining, a marker of the oxidative profile of individual fibers, was also increased in transversal skeletal muscle sections of white gastrocnemius muscle from Tg-AMPKgamma3(225Q) mice, independent of changes in fiber type composition. In conclusion, a single nucleotide mutation (R225Q) in the AMPK gamma3 subunit is associated with mitochondrial biogenesis in glycolytic skeletal muscle, concomitant with increased expression of the co-activator PGC-1alpha and several transcription factors that regulate mitochondrial proteins, without altering fiber type composition.

Neuromuscular junctions are more sensitive to onset of aging than myofibers

Sarcopenia has been linked to a host of health problems including osteoporosis, accidental falls, and type II diabetes. Denervation may precipitate the loss in muscle size and change in fiber type distribution characterizing sarcopenia. This study aimed to determine whether remodeling of the neuromuscular junction (NMJ) preceded alterations in myofiber profile commonly observed with aging. Ten young (5 mo) and 10 moderately aged (22 mo) Fischer 344 rats were killed and plantaris muscles were removed, and frozen until analysis. To visualize NMJs, longitudinal muscle sections were doubly stained with rhodamine conjugated α‐bungarotoxin and fluorescein labeled RT‐97 antibody, which bind to postsynaptic acetylcholine receptors and presynaptic nerve terminal branches, respectively. Myofiber profiles were assessed with histochemical staining for mATPase activity of muscle cross‐sections. Compared to NMJs of young rats, those of moderately aged ones displayed significant (P&lt;0.05) remodeling including greater nerve terminal branch length and complexity of arborization, along with amplified perimeter length and area of staining at post‐synaptic endplates. In contrast, myofibers of aged rats showed no evidence of atrophy or changes in fiber type composition. These data show that age‐related alterations of the neuromuscular system are observed sooner in NMJs than in myofibers.

Dystrophin deficiency in canine X-linked muscular dystrophy in Japan (CXMDJ) alters myosin heavy chain expression profiles in the diaphragm more markedly than in the tibialis cranialis muscle

BackgroundSkeletal muscles are composed of heterogeneous collections of muscle fiber types, the arrangement of which contributes to a variety of functional capabilities in many muscle types. Furthermore, skeletal muscles can adapt individual myofibers under various circumstances, such as disease and exercise, by changing fiber types. This study was performed to examine the influence of dystrophin deficiency on fiber type composition of skeletal muscles in canine X-linked muscular dystrophy in Japan (CXMDJ), a large animal model for Duchenne muscular dystrophy.MethodsWe used tibialis cranialis (TC) muscles and diaphragms of normal dogs and those with CXMDJ at various ages from 1 month to 3 years old. For classification of fiber types, muscle sections were immunostained with antibodies against fast, slow, or developmental myosin heavy chain (MHC), and the number and size of these fibers were analyzed. In addition, MHC isoforms were detected by gel electrophoresis.ResultsIn comparison with TC muscles of CXMDJ, the number of fibers expressing slow MHC increased markedly and the number of fibers expressing fast MHC decreased with growth in the affected diaphragm. In populations of muscle fibers expressing fast and/or slow MHC(s) but not developmental MHC of CXMDJ muscles, slow MHC fibers were predominant in number and showed selective enlargement. Especially, in CXMDJ diaphragms, the proportions of slow MHC fibers were significantly larger in populations of myofibers with non-expression of developmental MHC. Analyses of MHC isoforms also indicated a marked increase of type I and decrease of type IIA isoforms in the affected diaphragm at ages over 6 months. In addition, expression of developmental (embryonic and/or neonatal) MHC decreased in the CXMDJ diaphragm in adults, in contrast to continuous high-level expression in affected TC muscle.ConclusionThe CXMDJ diaphragm showed marked changes in fiber type composition unlike TC muscles, suggesting that the affected diaphragm may be effectively adapted toward dystrophic stress by switching to predominantly slow fibers. Furthermore, the MHC expression profile in the CXMDJ diaphragm was markedly different from that in mdx mice, indicating that the dystrophic dog is a more appropriate model than a murine one, to investigate the mechanisms of respiratory failure in DMD.

Is Fiber-Type Composition Related to Daily Jaw Muscle Activity during Postnatal Development?

Aim: Muscles containing large numbers of slow-contracting fibers are generally more active than muscles largely composed of fast fibers. This relationship between muscle activity and phenotype suggests that (1) changes in fiber-type composition during postnatal development are accompanied by changes in daily activity and (2) individual variations in fiber-type composition are related to similar variations in daily muscle activity. Methods: The masseter and digastric muscles of 23 New Zealand White rabbits (young, juvenile and adult) were examined for their phenotype (myosin heavy chain content) and their daily activity (total daily number of activity bursts). Results: During development, the masseter showed a strong increase in the number of fast-type fibers compared to the number of slow-type fibers. During development, also the number of powerful bursts in the masseter increased. The digastric showed no significant changes in fiber types or burst numbers. Within each muscle, across individual animals, no significant correlations (R < 0.70) were found between any of the fiber types and daily burst numbers in any of the age groups. Conclusions: The results suggest that activity-related influences are of relatively minor importance during development and that other factors are dominant in determining fiber-type composition.