Muscle Ultrastructural Changes Research Articles

Restoring Mitochondrial Function and Muscle Satellite Cell Signaling: Remedies against Age-Related Sarcopenia.

Sarcopenia has a complex pathophysiology that encompasses metabolic dysregulation and muscle ultrastructural changes. Among the drivers of intracellular and ultrastructural changes of muscle fibers in sarcopenia, mitochondria and their quality control pathways play relevant roles. Mononucleated muscle stem cells/satellite cells (MSCs) have been attributed a critical role in muscle repair after an injury. The involvement of mitochondria in supporting MSC-directed muscle repair is unclear. There is evidence that a reduction in mitochondrial biogenesis blunts muscle repair, thus indicating that the delivery of functional mitochondria to injured muscles can be harnessed to limit muscle fibrosis and enhance restoration of muscle function. Injection of autologous respiration-competent mitochondria from uninjured sites to damaged tissue has been shown to reduce infarct size and enhance cell survival in preclinical models of ischemia-reperfusion. Furthermore, the incorporation of donor mitochondria into MSCs enhances lung and cardiac tissue repair. This strategy has also been tested for regeneration purposes in traumatic muscle injuries. Indeed, the systemic delivery of mitochondria promotes muscle regeneration and restores muscle mass and function while reducing fibrosis during recovery after an injury. In this review, we discuss the contribution of altered MSC function to sarcopenia and illustrate the prospect of harnessing mitochondrial delivery and restoration of MSCs as a therapeutic strategy against age-related sarcopenia.

Assessment of the Preventive Effect of L-carnitine on Post-statin Muscle Damage in a Zebrafish Model

Statins, such as lovastatin, are lipid-lowering drugs (LLDs) that have been used to treat hypercholesterolaemia, defined as abnormally elevated cholesterol levels in the patient’s blood. Although statins are considered relatively safe and well tolerated, recipients may suffer from adverse effects, including post-statin myopathies. Many studies have shown that supplementation with various compounds may be beneficial for the prevention or treatment of side effects in patients undergoing statin therapy. In our study, we investigated whether L-carnitine administered to zebrafish larvae treated with lovastatin alleviates post-statin muscle damage. We found that exposure of zebrafish larvae to lovastatin caused skeletal muscle disruption observed as a reduction of birefringence, changes in muscle ultrastructure, and an increase in atrogin-1. Lovastatin also affected heart performance and swimming behaviour of larvae. Our data indicated that the muscle-protective effect of L-carnitine is partial. Some observed myotoxic effects, such as disruption of skeletal muscle and increase in atrogin-1 expression, heart contraction could be rescued by the addition of L-carnitine. Others, such as slowed heart rate and reduced locomotion, could not be mitigated by L-carnitine supplementation.

Snow buntings preparing for migration increase muscle fiber size and myonuclear domain in parallel with a major gain in fat mass

In long‐distance migrants, preparation for migration is typically associated with increases in fat and body mass, and with an enlargement of pectoralis muscle mass that likely improves flight performance. Although changes in muscle mass or size have been well described in migratory birds, potential changes in muscle ultrastructure during this transition still deserves scrutiny. Using outdoor captive snow buntings (Plectrophenax nivalis n = 15) measured during their transition into a spring migratory phenotype as a model system, we studied changes in pectoralis muscle ultrastructure and predicted that muscle fiber diameter could increase in parallel with the gain in body mass. We also expected that larger fibers could either recruit satellite cells to support cellular maintenance and protein turnover, increase myonuclear domain (cytoplasm per nuclei) with a potential increase in protein turnover load per myonucleus, or existing myonuclei could undergo endoreduplication. Buntings increased body mass by 46% within a month, largely due to a > 6‐fold increase in body fat. However, this increase in body mass was also associated with a 36% increase in muscle fiber diameter. Both pectoralis muscle mass (r2 = 0.57–0.77) and fiber diameter (r2 = 0.32) correlated with total body mass, without any change in the number of nuclei per fiber. Consequently, variation in myonuclear domain (i.e. the amount of cytoplasm per nucleus), was also positively associated with body mass (r2 = 0.51). Therefore, buntings preparing for migration may experience an increase in muscle contraction force due to larger muscle fibers, but this is also coupled with increases in myonuclear domain, which may force these cells to increase protein production to safeguard satellite cells.

Consequences of being phenotypically mismatched with the environment: rapid muscle ultrastructural changes in cold-shocked black-capped chickadees (Poecile atricapillus).

Phenotypic flexibility has received considerable attention in the last decade; however, whereas many studies have reported amplitude of variation in phenotypic traits, much less attention has focused on the rate at which traits can adjust in response to sudden changes in the environment. We investigated whole animal and muscle phenotypic changes occurring in black-capped chickadees (Poecile atricapillus) acclimated to cold (-5°C) and warm (20°C) temperatures in the first 3 h following a 15°C temperature drop (over 3 h). Before the temperature change, cold-acclimated birds were consuming 95% more food, were carrying twice as much body fat, and had 23% larger pectoralis muscle fiber diameters than individuals kept at 20°C. In the 3 h following the temperature drop, these same birds altered their pectoralis muscle ultrastructure by increasing the number of capillaries per fiber area and the number of nuclei per millimeter of fiber by 22%, consequently leading to a 22% decrease in myonuclear domain (amount of cytoplasm serviced per nucleus), whereas no such changes were observed in the warm-acclimated birds. To our knowledge, this is the first demonstration of such a rapid adjustment in muscle fiber ultrastructure in vertebrates. These results support the hypothesis that chickadees maintaining a cold phenotype are better prepared than warm-phenotype individuals to respond to a sudden decline in temperature, such as what may be experienced in their natural wintering environment.

Muscle myonuclear domain, but not oxidative stress, decreases with age in a long-lived seabird with high activity costs.

In birds, many physiological parameters appear to remain constant with increasing age, showing no deterioration until 'catastrophic' mortality sets in. Given their high whole-organism metabolic rate and the importance of flight in foraging and predator avoidance, flight muscle deterioration and accumulated oxidative stress and tissue deterioration may be an important contributor to physiological senescence in wild birds. As a by-product of aerobic respiration, reactive oxygen species are produced and can cause structural damage within cells. The anti-oxidant system deters oxidative damage to macromolecules. We examined oxidative stress and muscle ultrastructure in thick-billed murres aged 8 to 37 years (N=50) in pectoralis muscle biopsies. When considered in general linear models with body mass, body size and sex, no oxidative stress parameter varied with age. In contrast, there was a decrease in myonuclear domain similar to that seen in human muscle aging. We conclude that for wild birds with very high flight activity levels, muscle ultrastructural changes may be an important contributor to demographic senescence. Such gradual, linear declines in muscle morphology may eventually contribute to 'catastrophic' failure in foraging or predator avoidance abilities, leading to demographic senescence.

Ultrastructural changes in human masseter muscles after botulinum neurotoxin a injection.

Botulinum neurotoxin A (BoNTA) has long been used as a therapeutic agent and has been widely accepted as a cosmetic agent in recent years. It can inhibit function and induce structural changes in skeletal muscle. Specimens of fresh dissected human masseter muscle were used to observe the ultrastructural changes that occurred at 6 and 12 months following BoNTA injection. The findings observed were muscle fiber distortion, sarcomere shortening, mitochondrial vacuolar degeneration, glycogen accumulation, and H and M band disruption in the triad of tubules. At 12 months after injection, there was still evidence of degenerative changes in muscle ultrastructure, whereas most organelles exhibited a normal structure. Profound ultrastructural and organelle disfiguring changes were observed after BoNTA injection into human masseter muscle. Most changes were transient, however, and were resolved by 12 months after injection. Muscle Nerve 57: 96-99, 2018.

From Molecules to Mating Success: Integrative Biology of Muscle Maturation in a Dragonfly

2 SYNOPSIS. Dragonflies begin adult life as comparatively weak fliers, then mature to become one of nature's ultimate flying machines. This ontogenetic transition provides an opportunity to investigate the relationship between life history, phenotypic plastic- ity, and changing ecological demands on organismal performance. Here we present an overview of a wide-ranging study of dragonfly muscle maturation that reveals i) ecological changes in the need for efficient versus high-performance flight, ii) organ- ism-level changes in performance, thermal physiology, locomotor mechanics, and en- ergy efficiency, iii) tissue-level changes in muscle ultrastructure and sensitivity to ac- tivation by calcium, and iv) molecular-level changes in the Lsoform composition of a calcium regulatory protein in flight muscle (troponin-T). We discuss how these phe- nomena may be causally related, and thereby begin to show linkages across many levels of biological organization. In particular, we suggest that alternative splicing of troponin-T mRNA is an important component of the of muscle contractile function for developmental changes in wingbeat frequency and ecological demands on flight performance. Age-variable gearing of muscle function allows energetically eco- nomical flight during early adult growth, whereas power output is maximized at ma- turity when aerial competition determines success during territoriality and mating.

Muscle ultrastructural changes in long-standing idiopathic total facial nerve palsy.

Total facial palsy may be idiopathic, iatrogenic, traumatic, or caused by inflammatory, viral, or tumoral diseases. In these cases, the loss of facial movements may be irreversible and the only possible chance for the patients is a surgical procedure. Facial muscle reinnervation procedures may be effective even when performed years after the onset of the paralysis. One of the factors that must be considered in planning this surgery is the capacity of the muscle fibers to regain their contractile action. In the present study, the ultrastructural changes of the denervated muscle (auricularis posterior muscle) in cases of long-standing idiopathic facial nerve paralysis are evaluated.

NOTES: Small Differences in Drosophila Tropomyosin Expression Have Significant Effects on Muscle Function

The effects of promoter deletions on Drosophila tropomyosin I (TmI) gene expression have been determined by measuring TmI RNA levels in transformed flies. Decreases in RNA levels have been correlated with rescue of flightless and jumpless mutant phenotypes in Ifm(3)3 mutant transformed flies and changes in muscle ultrastructure. The results of this analysis have allowed us to identify a region responsible for 20% of maximal TmI expression, estimate threshold levels of TmI RNA required for indirect flight and jump muscle function, and obtain evidence suggesting that sarcomere length may be an important determinant of flight muscle function.

Small differences in Drosophila tropomyosin expression have significant effects on muscle function.

The effects of promoter deletions on Drosophila tropomyosin I (TmI) gene expression have been determined by measuring TmI RNA levels in transformed flies. Decreases in RNA levels have been correlated with rescue of flightless and jumpless mutant phenotypes in Ifm(3)3 mutant transformed flies and changes in muscle ultrastructure. The results of this analysis have allowed us to identify a region responsible for 20% of maximal TmI expression, estimate threshold levels of TmI RNA required for indirect flight and jump muscle function, and obtain evidence suggesting that sarcomere length may be an important determinant of flight muscle function.

Muscle lipofuscin content and satellite cell volume is increased after high altitude exposure in humans

Muscle ultrastructural changes during a typical expedition to the Himalayas were analyzed by taking muscle biopsies from seven climbers before and after their sojourn at high altitude (over 5000 m for 8 weeks). M. vastus lateralis samples were analyzed morphometrically from electron micrographs. A quantitative evaluation was made of lipofuscin, satellite cells and myonuclei. Significant increases of the volume densities of lipofuscin (+ 235%) and satellite cells (+ 215%) were observed.

Muscle Ultrastructural Changes in Freshwater Prawns, Macrobrachium rosenbergii during Iced Storage

ABSTRACTDeheaded and whole prawns (Macrobrachium rosenbergii) were stored up to 10 days on ice. Myofibrils, extracted from the first abdominal segment, were prepared for incubations at different ionic strengths (0.1 to 0.3 M) and subsequent SDS‐gel electrophoresis, while other samples were prepared intact for transmission election microscopy. Elevated ionic strengths in vitro increased the solubilization of specific myofibrillar proteins (such as myosin heavy chain); this effect was especially pronounced in prawns stored whole. Proteolysis was indicated in samples from whole prawns by the appearance of a family of proteins ranging in molecular weight from 65 kD to 180 kD. Loss of myofibrillar integrity was apparent by day 10, with losses more pronounced in whole prawns than in deheaded prawns.

Specificity of leg power changes to velocities used in bicycle endurance training.

Increases in leg power production resulting from 8 wk of bicycle endurance training (30 min/day, 5 times/wk) were studied using an isokinetic dynamometer. In addition, biopsies of vastus lateralis were analyzed to characterize muscle ultrastructural changes. Performance increased on the dynamometer specifically near the estimated average knee angular velocity used during the bicycle training (200 degrees/s). Power measurements were made during the first 5 contractions (maximal power: Pmax) and last 5 contractions (final power: Pend) of 25 and 50 consecutive contractions (at 60 and 240 degrees/s, respectively). Pmax and Pend increased only at 240 degrees/s but not at 60 degrees/s. These increases in Pmax (86 W) and Pend (78 W) resulted primarily from longer torque maintenance but also from increased peak torque during each contraction and were close to the increase in mechanical power output maintained on the bicycle (Pb; 78 W) during the training sessions. The specificity of these changes to the angular velocities used in the bicycle training indicates a neural basis to these adaptations. We suggest that these neural adaptations, coupled with the observed enhancement of muscle mitochondrial and capillary density (+41 and +15%, respectively) underlie the increased ability to maintain power production on a bicycle after endurance training.

Human Striated Muscle Ultrastructural Changes Accompanying Increased Strength without Hypertrophy

Abstract Skeletal muscle was obtained from the vastus lateralis of three normal college male students. Two biopsies were obtained prior to a training period and one after the training period. Subjects participated in an intense weight training program involving isometric and isotonic exercises. The subjects participated in the exercise regimen five days in each week for a period of 10 weeks. Muscle tissue was processed immediately for electron microscope examination. The following parameters were measured from micrographs of longitudinal sections: sarcomere length, sarcomere width, intracellular fat, mitochondria number and mitochondria length. The following parameters were measured from micrographs of cross sections: myosin filament concentration, distance between myosin filaments, myosin filament diameter, the number of actin filaments in orbit around a myosin filament, and gross cell size. Major findings included significant changes in myosin filament concentration, distance between myosin filaments, a...