Muscles, Volume 2, Issue 1 (March 2023) – 9 articles

Background: This study sought to investigate whether different physical function tests (objective measures of physical performance) may identify a low physical resilience in breast cancer survivors (BCS). Methods: This analytical cross-sectional study evaluated 146 BCS and 69 age-matched women without breast cancer history. The different times after the end of treatment were used as criteria for group division. Participants were divided into four groups: control (CT: n = 69–women without breast cancer history); <1.0 years after the end of treatment (<1 YAT: n = 60); 1–3.9 years after the end of treatment (1–3.9 YAT: n = 45); and ≥4 years after the end of treatment (>4 YAT: n = 41). Physical function was evaluated by 4 m walk test (4-MWT), five-times-sit-to-stand test (FTSST), timed up and go test (TUG), and short physical performance battery (SPPB). Age, menopausal status, smoking, number of medications, level of physical activity, body mass index, and muscle strength were used as confounding variables in ANCOVA. Results: All groups that underwent cancer treatment (<1 YAT, 1–3.9 YAT and ≥4 YAT) had lower physical performance (p < 0.001) identified by 4 MWT, TUG, and FTSST when compared to the CT group. For the SPPB, the <1 YAT and ≥4 YAT groups had lower performance (p = 0.005) when compared to the CT. Conclusions: The different physical function tests can be used to identify a low physical resilience in BCS. Full article

Skeletal muscle physiology is regulated by microRNA that are localized within skeletal muscle (myomiRs). This study investigated how the expression of myomiRs and genes regulating skeletal muscle mass and myogenesis are influenced in response to acute and consecutive days of exercise-related signaling using the exercise mimetic, formoterol, in vitro. Human skeletal muscle cells were proliferated and differentiated for 6 days. Experimental conditions included: (a) control, (b) acute formoterol stimulation (AFS), and (c) consecutive days of formoterol stimulation (CFS). For AFS, myotubes were treated with 30 nM of formoterol for three hours on day 6 of differentiation, and this was immediately followed by RNA extraction. For CFS, myotubes were treated with 30 nM of formoterol for three hours on two or three consecutive days, with RNA extracted immediately following the final three-hour formoterol treatment. We observed increased myomiR expression for both AFS and CFS. AFS appeared to promote myogenesis, but this effect was lost with CFS. Additionally, we observed increased expression of genes involved in metabolism, mitochondrial biogenesis, and muscle protein degradation in response to AFS. myomiR and gene expression appear to be sensitive to acute and long-term exercise-related stimuli, and this likely contributes to the regulation of skeletal muscle mass. Full article

The diagnosis of primary mitochondrial myopathy is often delayed by years due to non-specific clinical symptoms as well as variable testing of mitochondrial disorders. The aim of this review is to summarize and discuss the collective findings and novel insights regarding the diagnosing, testing, and clinical presentation of primary mitochondrial myopathy (PMM). PMM results from a disruption of the oxidative phosphorylation (OXPHOS) chain in mitochondria due to mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Although there are many named syndromes caused by mitochondrial mutations, this review will focus on PMM, which are mitochondrial disorders mainly affecting, but not limited to, the skeletal muscle. Clinical presentation may include muscle weakness, exercise intolerance, myalgia, and rhabdomyolysis. Although skeletal muscle and respiratory function are most frequently affected due to their high energy demand, multisystem dysfunction may also occur, which may lead to the inclusion of mitochondrial myopathies on the differential. Currently, there are no effective disease-modifying treatments, and treatment programs typically only focus on managing the symptomatic manifestations of the disease. Although the field has a large unmet need regarding treatment options, diagnostic pathways are better understood and can help shorten the diagnostic journey to aid in disease management and clinical trial enrollment. Full article

Amyotrophic lateral sclerosis (ALS) is a complex systemic disease that primarily involves motor neuron dysfunction and skeletal muscle atrophy. One commonly used mouse model to study ALS was generated by transgenic expression of a mutant form of human superoxide dismutase 1 (SOD1) gene harboring a single amino acid substitution of glycine to alanine at codon 93 (G93A*SOD1). Although mutant-SOD1 is ubiquitously expressed in G93A*SOD1 mice, a detailed analysis of the skeletal muscle expression pattern of the mutant protein and the resultant muscle pathology were never performed. Using different skeletal muscles isolated from G93A*SOD1 mice, we extensively characterized the pathological sequelae of histological, molecular, ultrastructural, and biochemical alterations. Muscle atrophy in G93A*SOD1 mice was associated with increased and differential expression of mutant-SOD1 across myofibers and increased MuRF1 protein level. In addition, high collagen deposition and myopathic changes sections accompanied the reduced muscle strength in the G93A*SOD1 mice. Furthermore, all the muscles in G93A*SOD1 mice showed altered protein levels associated with different signaling pathways, including inflammation, mitochondrial membrane transport, mitochondrial lipid uptake, and antioxidant enzymes. In addition, the mutant-SOD1 protein was found in the mitochondrial fraction in the muscles from G93A*SOD1 mice, which was accompanied by vacuolized and abnormal mitochondria, altered OXPHOS and PDH complex protein levels, and defects in mitochondrial respiration. Overall, we reported the pathological sequelae observed in the skeletal muscles of G93A*SOD1 mice resulting from the whole-body mutant-SOD1 protein expression. Full article

It is well known that muscular dystrophy disease severity is controlled by genetic modifiers. The expectation is that by identifying these modifiers, we can illuminate additional therapeutic targets with which to combat the disease. To this end we have been investigating the MRL mouse strain, which is highly resistant to muscular dystrophy-mediated fibrosis. The MRL mouse strain contains two mitochondrial-encoded, naturally occurring heteroplasmies: T3900C in tRNA-Met, and variable adenine insertions at 9821 in tRNA-Arg. Heteroplasmies are mitochondrial mutations that are variably present in a cell’s mitochondria. Therefore, MRL cells can contain 0 to 100% of each mitochondrial mutation. We have chosen the severely affected ϒ-sarcoglycan (Sgcg–/–) deficient mice on the DBA2/J background as our muscular dystrophy model to demonstrate the effects of these mitochondrial heteroplasmies on disease severity. Mice from the (Sgcg–/–) DBA2/J (D) and wildtype MRL (M) strains were crossed for more than 10 generations to establish two separate, pure breeding mouse lines: Sgcg+/–Nuc^DMito^%M and Sgcg+/–Nuc^MMito^%M. The Sgcg–/– mice from these separate lines were analyzed at 8 weeks old for membrane permeability, hydroxyproline content, pAMPK content, fibronectin content, and percentage of each heteroplasmy. We have identified that the MRL mitochondrial mutation T3900C confers a portion of the fibrosis resistance identified in the MRL mouse strain. These results have been extended to significantly correlate increased MRL mitochondria with increased pAMPK and decreased muscular dystrophy fibrosis. The beneficial mechanisms controlled by the MRL mitochondria will be discussed. We are establishing metabolic aspects of muscular dystrophy pathogenesis. These metabolic pathways will now be investigated for therapeutic targets. Full article

We have previously shown that hypothermia leads to an increase in the synaptic modulating effects of ATP but not of adenosine in several different animal skeletal muscles. In this paper, we studied the effect of ATP on the amplitude–time parameters of single and tetanic contractions of rats’ isolated fast (1) and slow (2) muscles at different temperatures. We found that when muscles were stimulated by the electrical field (0.1 Hz, 0.5 ms, 10 V), with a decrease in the bath temperature from 37 °C to 14 °C (3), there was an increase in the half-relaxation time of the slow muscle (m. soleus), but not of the fast muscle (m. EDL). Similar effects were observed using a carbachol-induced contraction technique, which suggests the postsynaptic (4) nature of the expansion of the contractile response of the slow muscle induced by ATP (5). To confirm the postsynaptic nature of the observed phenomenon, experiments were performed at a high calcium level (7.2 mM), in which the presynaptic effects of ATP were shown to be offset. We found that the hypercalcium condition did not significantly change the effects of ATP on the measured parameters in both muscles. To record muscle tetanic contractions, we gradually increased the frequency of electrical impulses with the increment of 2.5 Hz to achieve the fusion frequencies of 12.5 Hz for m. soleus and 17.5 Hz for m. EDL at normal temperatures. ATP (100 μM) did not change the fusion frequency for both muscles at a normal temperature but decreased this parameter for the slow muscle to 5 Hz at 14 °C without affecting that for the fast muscle. We conclude that ATP potentiates a hypothermia-induced increase in the half-relaxation time of the contraction of rats’ slow, but not fast, skeletal muscles by acting on postsynaptic P2 receptors (6). Full article

Purpose: To analyze the muscle activation of the rectus femoris (RF), vastus lateralis (VL), gluteus maximus (GM), and biceps femoris (BF) in concentric and eccentric actions in the squat at 90° and 140° range of motion. Methods: Thirty-five women (32.9 ± 7.4 years; 64.5 ± 11.5 kg; 1.63 ± 0.1 m; BMI: 24.2 ± 2.9 kg/m²; %fat: 24.9 ± 6.5%) experienced exercise for at least eight weeks. Electrodes were positioned in standardized locations. The signals were acquired by an A/D SAS1000 V8 converter and the electromyographic activity normalized in the percentage of the highest produced value (%RMS). The data were analyzed using repeated measures two-way ANOVA, with effect size (η²) and differences calculated in percentage points (∆ p.p.). Results: The RF (p = 0.001; ∆ = 5.1 p.p.) and BF activation (p = 0.020; ∆ = 4.0 p.p.) was higher at 90° in the eccentric action. The RF showed an interaction between the range of motion and %RMS, with a large effect size (F = 37.9; p = 0.001; η² = 0.485). The VL activation was higher at 140° (p = 0.005; ∆ = 3.9 p.p.) in the concentric action and higher at 90° (p = 0.006; ∆ = 3.7 p.p.) in the eccentric action, with a large effect size significant interaction (F = 21.3; p = 0.001; η² = 0.485). The GM activation was higher at 90° in the concentric (p = 0.020; ∆ = 5.4 p.p.) and eccentric action (p = 0.022; ∆ = 41 p.p.). Conclusions: The biarticular muscles were influenced by the squat range only in the eccentric action of the movement, while the monoarticular muscles were influenced by the squat in both concentric and eccentric muscle action. Full article

(1) Introduction: Soccer players face high demand for training and games. To facilitate their performance, many studies have investigated ergogenic supplements that can assist in the recovery and performance of players. The aim of this research was to assess whether caffeine supplementation can help soccer players’ recovery and performance. (2) Methods: Professional players were given 210 mg of caffeine or placebo in seven games during the state championship, being offered placebo in three matches and caffeine in four matches, administered 30 min before the game, during the game, and after the game. Blood creatine kinase (CK) and heart rate variability (HRV) were measured. Participants rated their perceived recuperation (RPR) and exertion (RPE) on scales developed by Laurent and Borg, respectively. The time that the player spent on the field was also evaluated. t-tests and Levene’s test were used to analyze the results. In addition to mean differences, variations in the results were also analyzed. (3) Results: No significant differences were found in CK, HRV, RPR, RPE, or minutes on the field when comparing caffeine supplementation with the placebo. (4) Conclusion: Caffeine supplementation throughout the championship appears to have had no ergogenic effect on athlete performance and recovery. Full article