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This study investigated the coactivation of plantar flexor and dorsiflexor muscles and oxygen uptake during running with forefoot and rearfoot strikes at 15 and 19 km/h. We included 16 male runners in this study. The participants ran each foot strike pattern for 5 min at 15 and 19 km/h on a treadmill. During the running, respiratory gas exchange data and surface electromyographic (EMG) activity of the medial gastrocnemius (MG), lateral gastrocnemius (LG), soleus, and tibialis anterior muscles of the right lower limb were continuously recorded. The indices of oxygen uptake, energy expenditure (EE), and muscle activation were calculated during the last 2 min in each condition. During the stance phase of running at 15 and 19 km/h, activation of the tibialis anterior and MG muscles was lower and higher, respectively, with forefoot strike than with rearfoot strike. The foot strike pattern did not influence the oxygen uptake. These results suggest that the foot strike pattern has no clear effect on the oxygen uptake when running at 15 and 19 km/h. However, forefoot strike leads to plantar flexion dominance during co‐contraction of the tibialis anterior and MG muscles, which are an antagonist and agonist for plantar flexion, respectively, during the stance phase. [ABSTRACT FROM AUTHOR]

The dystrophin protein has well‐characterized roles in force transmission and maintaining membrane integrity during muscle contraction. Studies have reported decreased expression of dystrophin in atrophying muscles during wasting conditions, and that restoration of dystrophin can attenuate atrophy, suggesting a role in maintaining muscle mass. Phosphorylation of S3059 within the cysteine‐rich region of dystrophin enhances binding between dystrophin and β‐dystroglycan, and mimicking phosphorylation at this site by site‐directed mutagenesis attenuates myotube atrophy in vitro. To determine whether dystrophin phosphorylation can attenuate muscle wasting in vivo, CRISPR‐Cas9 was used to generate mice with whole body mutations of S3059 to either alanine (DmdS3059A) or glutamate (DmdS3059E), to mimic a loss of, or constitutive phosphorylation of S3059, on all endogenous dystrophin isoforms, respectively. Sciatic nerve transection was performed on these mice to determine whether phosphorylation of dystrophin S3059 could attenuate denervation atrophy. At 14 days post denervation, atrophy of tibialis anterior (TA) but not gastrocnemius or soleus muscles, was partially attenuated in DmdS3059E mice relative to WT mice. Attenuation of atrophy was associated with increased expression of β‐dystroglycan in TA muscles of DmdS3059E mice. Dystrophin S3059 phosphorylation can partially attenuate denervation‐induced atrophy, but may have more significant impact in less severe modes of muscle wasting. [ABSTRACT FROM AUTHOR]

Lymphatic vessels are actively involved in the recovery process of inflamed tissues. However, the changes in intramuscular lymphatic vessels during inflammation caused by skeletal muscle injury remain unclear. Therefore, the purpose of this study was to clarify the changes in lymphatic vessels after skeletal muscle injury. The left tibialis anterior muscles of male mice were subjected to lengthening contractions (LC) for inducing skeletal muscle injury, and samples were collected on Days 2, 4, and 7 for examining changes in both the skeletal muscles and intramuscular lymphatic vessels. With hematoxylin–eosin staining, the inflammatory response was observed in myofibers on Days 2 and 4 after LC, whereas regeneration of myofibers was found on Day 7 after LC. The number and area of intramuscular lymphatic vessels analyzed by immunohistochemical staining with an antibody against lymphatic vessel endothelial hyaluronan receptor 1 were significantly increased only on Day 4 after LC. Based on the abovementioned results, intramuscular lymphatic vessels undergo morphological changes such as increase under the state of muscle inflammation. This study demonstrated that the morphology of intramuscular lymphatic vessels undergoes significant changes during the initial recovery phase following skeletal muscle injury. [ABSTRACT FROM AUTHOR]

This study aimed to determine effects of cooling on contraction‐induced peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) and vascular endothelial growth factor (VEGF) gene expression, phosphorylations of its related protein kinases, and metabolic responses. Male rats were separated into two groups; room temperature (RT) or ice‐treated (COLD) on the right tibialis anterior (TA). The TA was contracted isometrically using nerve electrical stimulation (1‐s stimulation × 30 contractions, with 1‐s intervals, for 10 sets with 1‐min intervals). The TA was treated before the contraction and during 1‐min intervals with an ice pack for the COLD group and a water pack at RT for the RT group. The muscle temperature of the COLD group decreased to 19.42 ± 0.44°C (p < 0.0001, −36.4%) compared with the RT group after the experimental protocol. An increase in mRNA expression level of PGC‐1α, not VEGF, after muscle contractions was significantly lower in the COLD group than in the RT group (p < 0.0001, −63.0%). An increase in phosphorylated AMP‐activated kinase (AMPK) (p = 0.0037, −28.8%) and a decrease in glycogen concentration (p = 0.0231, +106.3%) after muscle contraction were also significantly inhibited by cooling. Collectively, muscle cooling attenuated the post‐contraction increases in PGC‐1α mRNA expression coinciding with decreases in AMPK phosphorylation and glycogen degradation. [ABSTRACT FROM AUTHOR]

Transcutaneous spinal cord stimulation (TSS) is purported to improve motor function in people after spinal cord injury (SCI). However, several methodology aspects are yet to be explored. We investigated whether stimulation configuration affected the intensity needed to elicit spinally evoked motor responses (sEMR) in four lower limb muscles bilaterally. Also, since stimulation intensity for therapeutic TSS (i.e., trains of stimulation, typically delivered at 15–50 Hz) is sometimes based on the single‐pulse threshold intensity, we compared these two stimulation types. In non‐SCI participants (n = 9) and participants with a SCI (n = 9), three different electrode configurations (cathode–anode); L1‐midline (below the umbilicus), T11‐midline and L1‐ASIS (anterior superior iliac spine; non‐SCI only) were compared for the sEMR threshold intensity using single pulses or trains of stimulation which were recorded in the vastus medialis, medial hamstring, tibialis anterior, medial gastrocnemius muscles. In non‐SCI participants, the L1‐midline configuration showed lower sEMR thresholds compared to T11‐midline (p = 0.002) and L1‐ASIS (p < 0.001). There was no difference between T11‐midline and L1‐midline for participants with SCI (p = 0.245). Spinally evoked motor response thresholds were ~13% lower during trains of stimulation compared to single pulses in non‐SCI participants (p < 0.001), but not in participants with SCI (p = 0.101). With trains of stimulation, threshold intensities were slightly lower and the incidence of sEMR was considerably lower. Overall, stimulation threshold intensities were generally lower with the L1‐midline electrode configuration and is therefore preferred. While single‐pulse threshold intensities may overestimate threshold intensities for therapeutic TSS, tolerance to trains of stimulation will be the limiting factor in most cases. [ABSTRACT FROM AUTHOR]

Skeletal muscle adapts to aerobic exercise training, in part, through fast‐to‐slow phenotypic shifts and an expansion of mitochondrial networks. Recent research suggests that the local and systemic benefits of exercise training also may be modulated by the mitochondrial‐derived peptide, MOTS‐c. Using a combination of acute and chronic exercise challenges, the goal of the present study was to characterize the interrelationship between MOTS‐c and exercise. Compared to sedentary controls, 4–8 weeks of voluntary running increased MOTS‐c protein expression ~1.5‐5‐fold in rodent plantaris, medial gastrocnemius, and tibialis anterior muscles and is sustained for 4–6 weeks of detraining. This MOTS‐c increase coincides with elevations in mtDNA reflecting an expansion of the mitochondrial genome to aerobic training. In a second experiment, a single dose (15 mg/kg) of MOTS‐c administered to untrained mice improved total running time (12% increase) and distance (15% increase) during an acute exercise test. In a final experiment, MOTS‐c protein translocated from the cytoplasm into the nucleus in two of six mouse soleus muscles 1 h following a 90‐min downhill running challenge; no nuclear translocation was observed in the plantaris muscles from the same animals. These findings indicate that MOTS‐c protein accumulates within trained skeletal muscle likely through a concomitant increase in mtDNA. Furthermore, these data suggest that the systemic benefits of exercise are, in part, mediated by an expansion of the skeletal muscle‐derived MOTS‐c protein pool. The benefits of training may persist into a period of inactivity (e.g., detraining) resulting from a sustained increase in intramuscular MOTS‐c proteins levels. [ABSTRACT FROM AUTHOR]

Abstract Skeletal muscle adapts to aerobic exercise training, in part, through fast‐to‐slow phenotypic shifts and an expansion of mitochondrial networks. Recent research suggests that the local and systemic benefits of exercise training also may be modulated by the mitochondrial‐derived peptide, MOTS‐c. Using a combination of acute and chronic exercise challenges, the goal of the present study was to characterize the interrelationship between MOTS‐c and exercise. Compared to sedentary controls, 4–8 weeks of voluntary running increased MOTS‐c protein expression ~1.5‐5‐fold in rodent plantaris, medial gastrocnemius, and tibialis anterior muscles and is sustained for 4–6 weeks of detraining. This MOTS‐c increase coincides with elevations in mtDNA reflecting an expansion of the mitochondrial genome to aerobic training. In a second experiment, a single dose (15 mg/kg) of MOTS‐c administered to untrained mice improved total running time (12% increase) and distance (15% increase) during an acute exercise test. In a final experiment, MOTS‐c protein translocated from the cytoplasm into the nucleus in two of six mouse soleus muscles 1 h following a 90‐min downhill running challenge; no nuclear translocation was observed in the plantaris muscles from the same animals. These findings indicate that MOTS‐c protein accumulates within trained skeletal muscle likely through a concomitant increase in mtDNA. Furthermore, these data suggest that the systemic benefits of exercise are, in part, mediated by an expansion of the skeletal muscle‐derived MOTS‐c protein pool. The benefits of training may persist into a period of inactivity (e.g., detraining) resulting from a sustained increase in intramuscular MOTS‐c proteins levels.

Functional interaction between the selective water channel AQP4 and several ion channels, such as TRPV4, NKCC1, and Na+/K+‐ATPase, closely participate to regulate osmotic homeostasis. In the skeletal muscles, the decrease in APQ4 expression due to denervation was followed by the restoration of AQP4 expression during reinnervation. These findings raised the possibility that innervation status is an essential factor to regulate AQP4 expression in the skeletal muscles. This study investigated this hypothesis using disuse muscle atrophy model with innervation. Adult female Fischer 344 rats (8 weeks of age) were randomly assigned to either control (C) or cast immobilization (IM) groups (n = 6 per group). Two weeks after cast immobilization, the tibialis anterior muscles of each group were removed and the expression levels of some target proteins were quantified by western blot analysis. The expression level of AQP4 significantly decreased at 2 weeks post‐immobilization (p < 0.05). Moreover, the expression levels of TRPV4, NKCC1, and Na+/K+‐ATPase significantly decreased at 2 weeks post‐immobilization (p < 0.05). This study suggested that innervation status is not always a key regulatory factor to maintain the expression of AQP4 in the skeletal muscles. Moreover, the transport of water and ions by AQP4 may be changed during immobilization‐induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Fucoidan is a sulfated polysaccharide found in a range of brown algae species. Growing evidence supports the long‐term supplementation of fucoidan as an ergogenic aid to improve skeletal muscle performance. The aim of this study was to investigate the effect of fucoidan on the skeletal muscle of mice. Male BL/6 mice (N = 8–10) were administered a novel fucoidan blend (FUC, 400 mg/kg/day) or vehicle (CON) for 4 weeks. Treatment and control experimental groups were further separated into exercise (CON+EX, FUC+EX) or no‐exercise (CON, FUC) groups, where exercised groups performed 30 min of treadmill training three times per week. At the completion of the 4‐week treatment period, there was a significant increase in cross‐sectional area (CSA) of muscle fibers in fucoidan‐treated extensor digitorum longus (EDL) and soleus fibers, which was accompanied by a significant increase in tibialis anterior (TA) muscle force production in fucoidan‐treated groups. There were no significant changes in grip strength or treadmill time to fatigue, nor was there an effect of fucoidan or exercise on mass of TA, EDL, or soleus muscles. In gastrocnemius muscles, there was no change in mRNA expression of mitochondrial biogenesis markers PGC‐1α and Nrf‐2 in any experimental groups; however, there was a significant effect of fucoidan supplementation on myosin heavy chain (MHC)‐2x, but not MHC‐2a, mRNA expression. Overall, fucoidan increased muscle size and strength after 4 weeks of supplementation in both exercised and no‐exercised mice suggesting an important influence of fucoidan on skeletal muscle physiology. [ABSTRACT FROM AUTHOR]

Aim: Cutaneous feedback from the foot sole contributes to the control of standing balance in two ways: it provides perceptual awareness of tactile perturbations at the interface with the ground (e.g., shifts in the pressure distribution, slips, etc.) and it reflexively activates lower‐motor neurons to trigger stabilizing postural responses. Here we focus on the latter, cutaneous (or cutaneomotor) reflex coupling in the lower limb. These reflexes have been studied most‐frequently with electrical pulse trains that bypass natural cutaneous mechanotransduction, stimulating cutaneous afferents in a largely non‐physiological manner. Harnessing the mechanical filtering properties of cutaneous afferents, we take a novel mechanical approach by applying supra‐threshold continuous noisy vibrotactile stimulation (NVS) to the medial forefoot. Methods: Using NVS, we characterized the time and frequency domain properties of cutaneomotor reflexes in the Tibialis Anterior. We additionally measured stimulus‐triggered average muscle responses to repeated discrete sinusoidal pulses for comparison. To investigate cutaneomotor reflex gain scaling, stimuli were delivered at 3‐ or 10‐times perceptual threshold (PT), while participants held 12.5% or 25% of maximum voluntary contraction (MVC). Results: Peak responses in the time domain were observed at lags reflecting transmission delay through a polysynaptic reflex pathway (~90–100 ms). Increasing the stimulus amplitude enhanced cutaneomotor coupling, likely by increasing afferent firing rates. Although greater background muscle contraction increased the overall amplitude of the evoked responses, it did not increase the proportion of the muscle response attributable to cutaneous input. Conclusion: Taken together, our findings support the use of NVS as a novel tool for probing the physiological properties of cutaneomotor reflex pathways. [ABSTRACT FROM AUTHOR]

B6.A-Dysfprmd/GeneJ (BLAJ) mice model human limb-girdle muscular dystrophy 2B (LGMD2B), which is linked to mutations in the dysferlin (DYSF) gene. We tested the hypothesis that, the calcium ion (Ca2+) channel blocker diltiazem (DTZ), reduces contraction-induced skeletal muscle damage, in BLAJ mice. We randomly assigned mice (N = 12; 3-4 month old males) to one of two groups - DTZ (N = 6) or vehicle (VEH, distilled water, N = 6). We conditioned mice with either DTZ or VEH for 1 week, after which, their tibialis anterior (TA) muscles were tested for contractile torque and susceptibility to injury from forced eccentric contractions. We continued dosing with DTZ or VEH for 3 days following eccentric contractions, and then studied torque recovery and muscle damage. We analyzed contractile torque before eccentric contractions, immediately after eccentric contractions, and at 3 days after eccentric contractions; and counted damaged fibers in the injured and uninjured TA muscles. We found that DTZ improved contractile torque before and immediately after forced eccentric contractions, but did not reduce delayed-onset muscle damage that was observed at 3 days after eccentric contractions. [ABSTRACT FROM AUTHOR]

When we walk in a challenging environment, we use visual information to modify our gait and place our feet carefully on the ground. Here, we explored how central common drive to ankle muscles changes in relation to visually guided foot placement. Sixteen healthy adults aged 23 ± 5 years participated in the study. Electromyography (EMG) from the Soleus (Sol), medial Gastrocnemius (MG), and the distal and proximal ends of the Tibialis anterior (TA) muscles and electroencephalography (EEG) from Cz were recorded while subjects walked on a motorized treadmill. A visually guided walking task, where subjects received visual feedback of their foot placement on a screen in realtime and were required to place their feet within narrow preset target areas, was compared to normal walking. There was a significant increase in the central common drive estimated by TA-TA and Sol-MG EMG-EMG coherence in beta and gamma frequencies during the visually guided walking compared to normal walking. EEG-TA EMG coherence also increased, but the group average did not reach statistical significance. The results indicate that the corticospinal tract is involved in modifying gait when visually guided placement of the foot is required. These findings are important for our basic understanding of the central control of human bipedal gait and for the design of rehabilitation interventions for gait function following central motor lesions. [ABSTRACT FROM AUTHOR]

Abstract This study tested the hypothesis that the ratio of changes in muscle fascicle and tendon length that occurs with joint movement scales linearly with the ratio of the slack lengths of the muscle fascicles and tendons. We compared the contribution of muscle fascicles to passive muscle‐tendon lengthening in muscles with relatively short and long fascicles. Fifteen healthy adults participated in the study. The medial gastrocnemius, tibialis anterior, and brachialis muscle‐tendon units were passively lengthened by slowly rotating the ankle or elbow. Change in muscle fascicle length was measured with ultrasonography. Change in muscle‐tendon length was calculated from estimated muscle moment arms. Change in tendon length was calculated by subtracting change in fascicle length from change in muscle‐tendon length. The median (IQR) contribution of muscle fascicles to passive lengthening of the muscle‐tendon unit, measured as the ratio of the change in fascicle length to the change in muscle‐tendon unit length, was 0.39 (0.26–0.48) for the medial gastrocnemius, 0.51 (0.29–0.60) for tibialis anterior, and 0.65 (0.49–0.90) for brachialis. Brachialis muscle fascicles contributed to muscle‐tendon unit lengthening significantly more than medial gastrocnemius muscle fascicles, but less than would be expected if the fascicle contribution scaled linearly with the ratio of muscle fascicle and tendon slack lengths.

This study tested the hypothesis that the ratio of changes in muscle fascicle and tendon length that occurs with joint movement scales linearly with the ratio of the slack lengths of the muscle fascicles and tendons. We compared the contribution of muscle fascicles to passive muscle-tendon lengthening in muscles with relatively short and long fascicles. Fifteen healthy adults participated in the study. The medial gastrocnemius, tibialis anterior, and brachialis muscle-tendon units were passively lengthened by slowly rotating the ankle or elbow. Change in muscle fascicle length was measured with ultrasonography. Change in muscle-tendon length was calculated from estimated muscle moment arms. Change in tendon length was calculated by subtracting change in fascicle length from change in muscle-tendon length. The median (IQR) contribution of muscle fascicles to passive lengthening of the muscle-tendon unit, measured as the ratio of the change in fascicle length to the change in muscle-tendon unit length, was 0.39 (0.26-0.48) for the medial gastrocnemius, 0.51 (0.29-0.60) for tibialis anterior, and 0.65 (0.49-0.90) for brachialis. Brachialis muscle fascicles contributed to muscle-tendon unit lengthening significantly more than medial gastrocnemius muscle fascicles, but less than would be expected if the fascicle contribution scaled linearly with the ratio of muscle fascicle and tendon slack lengths. [ABSTRACT FROM AUTHOR]

Continuous intramuscular stimulation of tibialis anterior (TA) was used to test the hypothesis that irregular trains of stimuli can increase force production and offset the magnitude of fatigue when compared with a continuous train of regular stimuli at an identical mean frequency (19 or 24 Hz). To achieve this, tungsten microelectrodes were inserted into the muscle belly into the motor point of the tibialis anterior muscle of able-bodied individuals (aged 19-50) and stimulated at current intensities ranging from 5 to 7 mA. The motor point was stimulated with a continuous train of regular stimulation at either 19 or 24 Hz (n = 11) or until the force declined below 25% of the peak force at the onset of stimulation. For the first seven subjects, no fatigue was exhibited, and thus, we simply compared the forces generated by the regular and irregular segments of the continuous train (120 sec for each segment). For four additional subjects, we delivered a higher frequency train (24 Hz) that elicited some fatigue. Once the force had declined below 25% of the initial peak force (which took between 140 and 210 sec), the continuous irregular train was integrated. Interestingly, for those subjects who exhibited muscular fatigue, force always began to rise again once the irregularity was incorporated into the continuous regular train of stimulation at the identical mean frequency (24 Hz). We conclude that incorporating irregularity into continuous trains of stimuli offers a significant advantage to the human neuromuscular system during both fatigued and nonfatigued states and could offer benefits to therapies such as functional electrical stimulation (FES). [ABSTRACT FROM AUTHOR]

Tensile-force transmitted by the tibialis anterior (TA) tendon of 11 anesthetized adult male Wistar rats (body-mass: 360.6 ± 66.3 g) was measured insitu within the intact biomechanical system of the hind-limb using a novel miniature in-line load-cell. The aim was to demonstrate the dependence of the loading-profile experienced by the muscle, on stimulation-frequency and the resistance to shortening in a group of control-animals. Data from these acute-experiments shows the type of loading achievable by means of implantable electrical stimulators activating agonists or agonist/antagonist groups of muscles during programmed resistance-training in freely moving healthy subjects. Force-responses to electrical stimulation of the common peroneal nerve for single pulses and short bursts were measured in unloaded and isometric contractions. A less time-consuming approach to measure the force-frequency relationship was investigated by applying single bursts containing a series of escalating stimulus-frequencies. We also measured the range of loading attainable by programmed co-contraction of the TA-muscle with the plantar-flexor muscles for various combinations of stimulation-frequencies. The maximal average peak-force of single twitches was 179% higher for isometric than for unloaded twitches. Average maximal isometric tetanic-force per gramme muscle-mass was 16.5 ± 3.0 N g-1, which agrees well with other studies. The standard and time-saving approaches to measure the force-frequency relationship gave similar results. Plantar-flexor co-activation produced greatly increased tension in the TA-tendon, similar to isometric contractions. Our results suggest that unloaded contractions may not be adequate for studies of resistance-training. Plantar-flexor co-contractions produced considerably higher force-levels that may be better suited to investigate the physiology and cell-biology of resistance-training in rodents. [ABSTRACT FROM AUTHOR]

Musculoskeletal (dys-)function relies for a large part on muscle architecture which can be obtained using Diffusion-Tensor MRI (DT-MRI) and fiber tractography. However, reconstructed tracts often continue along the tendon or aponeurosis when using conventional methods, thus overestimating fascicle lengths. In this study, we propose a new method for semiautomatic segmentation of tendinous tissue using tract density (TD). We investigated the feasibility and repeatability of this method to quantify the mean fascicle length per muscle. Additionally, we examined whether the method facilitates measuring changes in fascicle length of lower leg muscles with different foot positions. Five healthy subjects underwent two DT-MRI scans of the right lower leg, with the foot in 15° dorsiflexion, neutral, and 30° plantarflexion positions. Repeatability of fascicle length measurements was assessed using Bland-Altman analysis. Changes in fascicle lengths between the foot positions were tested using a repeated multivariate analysis of variance (MANOVA). Bland-Altman analysis showed good agreement between repeated measurements. The coefficients of variation in neutral position were 8.3, 16.7, 11.2, and 10.4% for soleus (SOL), fibularis longus (FL), extensor digitorum longus (EDL), and tibialis anterior (TA), respectively. The plantarflexors (SOL and FL) showed significant increase in fascicle length from plantarflexion to dorsiflexion, whereas the dorsiflexors (EDL and TA) exhibited a significant decrease. The use of a tract density for semiautomatic segmentation of tendinous structures provides more accurate estimates of the mean fascicle length than traditional fiber tractography methods. The method shows moderate to good repeatability and allows for quantification of changes in fascicle lengths due to passive stretch. [ABSTRACT FROM AUTHOR]

Muscle motor unit numbers decrease markedly in old age, while remaining motor units are enlarged and can have reduced neuromuscular junction transmission stability. However, it is possible that regular intense physical activity throughout life can attenuate this remodeling. The aim of this study was to compare the number, size, and neuromuscular junction transmission stability of tibialis anterior ( TA) motor units in healthy young and older men with those of exceptionally active master runners. The distribution of motor unit potential ( MUP) size was determined from intramuscular electromyographic signals recorded in healthy male Young (mean ± SD, 26 ± 5 years), Old (71 ± 4 years) and Master Athletes (69 ± 3 years). Relative differences between groups in numbers of motor units was assessed using two methods, one comparing MUP size and muscle cross-sectional area ( CSA) determined with MRI, the other comparing surface recorded MUPs with maximal compound muscle action potentials and commonly known as a 'motor unit number estimate ( MUNE)'. Near fiber ( NF) jiggle was measured to assess neuromuscular junction transmission stability. TA CSA did not differ between groups. MUNE values for the Old and Master Athletes were 45% and 40%, respectively, of the Young. Intramuscular MUPs of Old and Master Athletes were 43% and 56% larger than Young. NF jiggle was slightly higher in the Master Athletes, with no difference between Young and Old. These results show substantial and similar motor unit loss and remodeling in Master Athletes and Old individuals compared with Young, which suggests that lifelong training does not attenuate the age-related loss of motor units. [ABSTRACT FROM AUTHOR]

Results from imaging studies and finite element models suggest epimuscular myofascial effects on sarcomere lengths in series within muscle fibers. However, experimental evidence is lacking. We evaluated epimuscular myofascial effects on (1) muscle belly, fiber, and mean sarcomere length and (2) sarcomere length distribution within passive fibers of the rat tibialis anterior (TA) and soleus (SO) muscles. Hindlimbs (n = 24) were positioned in predefined knee (55°, 90°, 125°, 160°) and ankle (either 90° or 125°) angles, and fixed in a formaldehyde solution. Varying knee joint angle causes changes in muscle-tendon unit length of SO and TA's synergists, but not of SO and TA. Whole fibers were taken from SO and TA and photographed along their length. Mean sarcomere length was assessed for the entire fiber and for the proximal, intermediate, and distal thirds (fiber segments) separately. Mean sarcomere length of the fiber was not affected by knee angle, neither for SO (mean: 2.44 ± 0.03 μm and 2.19 ± 0.05 μm for ankle angles of 90° and 125°, respectively) nor for TA (mean: 2.33 ± 0.05 &956;m and 2.51 ± 0.07 μm for ankle angle set to 90° and 125°, respectively). Only for TA, a significant interaction between knee angle and fiber segment was found, indicating changes in the distribution of lengths of in-series sarcomeres. Thus, while epimuscular myofascial force transmission did not cause mean sarcomere length changes within passive SO and TA, it did alter the length distribution of sarcomeres within passive TA. [ABSTRACT FROM AUTHOR]

The spinal cord is extremely complex. Therefore, trans-spinal direct current stimulation (ts DCS) is expected to produce a multitude of neurophysiological changes. Here, we asked how ts DCS differentially affects synaptic and nonsynaptic transmission. We investigated the effects of ts DCS on synaptically mediated responses by stimulating the medullary longitudinal fascicle and recording responses in the sciatic nerve and triceps and tibialis anterior muscles. Response amplitude was increased during cathodal-ts DCS (c-ts DCS), but reduced during anodal-ts DCS (a-ts DCS). After-effects were dependent on the frequency of the test stimulation. c-ts DCS-reduced responses evoked by low-frequency (0.5 Hz) test stimulation and increased responses evoked by high-frequency (400 Hz) test stimulation. a-ts DCS had opposite effects. During and after c-ts DCS, excitability of the lateral funiculus tract ( LFT) and dorsal root fibers was increased. However, a-ts DCS caused a complex response, reducing the excitability of LFT and increasing dorsal root fiber responses. Local DC application on the sciatic nerve showed that the effects of DC on axonal excitability were dependent on polarity, duration of stimulation, temporal profile (during vs. after stimulation), orientation of the current direction relative to the axon and relative to the direction of action potential propagation, distance from the DC electrode, and the local environment of the nervous tissue. Collectively, these results indicate that synaptic as well as axonal mechanisms might play a role in ts DCS-induced effects. Therefore, this study identified many factors that should be considered in interpreting results of DCS and in designing ts DCS-based interventions. [ABSTRACT FROM AUTHOR]

Short-term consumption of a high-fat diet ( HFD) can result in an oxidative shift in adult skeletal muscle. However, the impact of HFD on young, growing muscle is largely unknown. Thus, 4-week-old mice were randomly divided into sedentary HFD (60% kcal from fat), sedentary standard chow (control), or exercise-trained standard chow. Tibialis anterior ( TA) and soleus muscles were examined for morphological and functional changes after 3 weeks. HFD consumption increased body and epididymal fat mass and induced whole body glucose intolerance versus control mice. Compared to controls, both HFD and exercise-trained TA muscles displayed a greater proportion of oxidative fibers and a trend for an increased succinate dehydrogenase ( SDH) content. The soleus also displayed an oxidative shift with increased SDH content in HFD mice. Despite the aforementioned changes, palmitate oxidation rates were not different between groups. To determine if the adaptive changes with HFD manifest as a functional improvement, all groups performed pre- and postexperiment aerobic exercise tests. As expected, exercise-trained mice improved significantly compared to controls, however, no improvement was observed in HFD mice. Interestingly, capillary density was lower in HFD muscles; a finding which may contribute to the lack of functional differences seen with HFD despite the oxidative shift in skeletal muscle morphology. Taken together, our data demonstrate that young, growing muscle exhibits early oxidative shifts in response to a HFD, but these changes do not translate to functional benefits in palmitate oxidation, muscle fatigue resistance, or whole body exercise capacity. [ABSTRACT FROM AUTHOR]

Skeletal muscle adapts to aerobic exercise training, in part, through fast-to-slow phenotypic shifts and an expansion of mitochondrial networks. Recent research suggests that the local and systemic benefits of exercise training also may be modulated by the mitochondrial-derived peptide, MOTS-c. Using a combination of acute and chronic exercise challenges, the goal of the present study was to characterize the interrelationship between MOTS-c and exercise. Compared to sedentary controls, 4-8 weeks of voluntary running increased MOTS-c protein expression ~1.5-5-fold in rodent plantaris, medial gastrocnemius, and tibialis anterior muscles and is sustained for 4-6 weeks of detraining. This MOTS-c increase coincides with elevations in mtDNA reflecting an expansion of the mitochondrial genome to aerobic training. In a second experiment, a single dose (15 mg/kg) of MOTS-c administered to untrained mice improved total running time (12% increase) and distance (15% increase) during an acute exercise test. In a final experiment, MOTS-c protein translocated from the cytoplasm into the nucleus in two of six mouse soleus muscles 1 h following a 90-min downhill running challenge; no nuclear translocation was observed in the plantaris muscles from the same animals. These findings indicate that MOTS-c protein accumulates within trained skeletal muscle likely through a concomitant increase in mtDNA. Furthermore, these data suggest that the systemic benefits of exercise are, in part, mediated by an expansion of the skeletal muscle-derived MOTS-c protein pool. The benefits of training may persist into a period of inactivity (e.g., detraining) resulting from a sustained increase in intramuscular MOTS-c proteins levels., (© 2022 The Author. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Clenbuterol induces a slow‐to‐fast fiber type transition in skeletal muscle. This muscle fiber transition decreased mitochondrial oxidative capacity and respiratory function. We hypothesized that the clenbuterol‐mediated reduction in oxidative capacity is associated with the alteration in mitochondrial morphology. To verify this hypothesis, we examined whether clenbuterol alters mitochondrial morphology and mitochondrial regulatory proteins in rat skeletal muscle. Clenbuterol was administered to rats via drinking water (30 mg/L) for 3 weeks. Myosin heavy chain (MHC) isoform composition, mitochondrial morphology, and fusion and fission regulatory protein levels in deep region and superficial region in tibialis anterior (TA) muscles were assessed. Clenbuterol induced the fiber type transition from slow to fast in both the regions of TA. The levels of optic atrophy protein 1, mitofusin 2, and mitochondrial fission 1, but not of dynamin‐related protein 1, significantly decreased in deep and superficial muscles after clenbuterol administration (P < 0.01). Also, observation using the transmission electron microscopy showed a decrease in mitochondrial volume (P < 0.05) and an increase in proportion of continuous or interacting mitochondria across Z‐lines (P < 0.05). We showed that clenbuterol administration induces a transition in the muscle fiber type composition toward fast phenotype and causes alterations in mitochondrial morphology with a concomitant decrease in mitochondrial fusion and fission regulatory protein levels. These mitochondrial morphological alterations may influence deleterious effects on skeletal muscle metabolism. [ABSTRACT FROM AUTHOR]

Determining a single compound maximal motor response (MMAX) or an average superimposed MMAX response (MSUP) are commonly used reference values in experiments eliciting raw electromyographic, motor evoked potentials, H‐reflexes, and V‐waves. However, existing literature is limited in detailing the most appropriate method to normalize these electrophysiological measures. Due to the accessibility of assessment from a cortical and spinal perspective, the tibialis anterior is increasingly used in literature and hence investigated in this study. The aims of the present study were to examine the differences and level of agreement in MMAX/MSUP under different muscle actions and contraction intensities. Following a familiarization session, 22 males visited the laboratory on a single occasion. MMAX was recorded under 10% isometric and 25% and 100% shortening and lengthening maximal voluntary contractions (MVC) at an angular velocity of 15° sec−1. MSUP was also recorded during 100% shortening and lengthening with an average of five responses recorded. There were no differences in MMAX or MSUP between contraction types. All variables showed large, positive correlations (P < 0.001, r2 ≥ 0.64). MMAX amplitude was larger (P < 0.001) at 100% shortening and lengthening intensity compared to MMAX amplitude at 10% isometric and 25% lengthening MVC. Bland‐Altman plots revealed a bias toward higher MMAX at the higher contraction intensities. Despite MSUP being significantly smaller than MMAX (P < 0.001) at 100% MVC, MSUP showed a large positive correlation (P < 0.001, r2 ≥ 0.64) with all variables. It is our recommendation that MMAX should be recorded at specific contraction intensity but not necessarily a specific contraction type. [ABSTRACT FROM AUTHOR]

Hoffmann (H‐) reflex amplitudes in plantar flexor soleus muscle are modulated by posture, yet dorsiflexor tibialis anterior (TA) H‐reflex parameters have sparingly been studied. The purpose was to investigate modulation of the TA H‐reflex when postural demands are increased from sitting to standing. In this study, data from 18 participants (Age: 25 ± 4 years, Height: 170.9 ± 9.5 cm, Weight: 75.9 ± 17.2 kg) allowed comparison of two experimental conditions involving different postures (i.e. sitting and standing). Maximal amplitude of the TA H‐reflex (Hmax) as a percent of the maximal M‐wave amplitude (Mmax) (Hmax (% Mmax)) during sitting and standing was compared using ANOVA. Modulation of TA H‐reflex amplitude was found: Eleven participants showed facilitation and seven showed no change of reflex amplitudes. Only participants in the facilitation group showed modulation related to changes in posture (sitting: 8.7 ± 2.9%; standing: 14.8 ± 6.7%, P = 0.005). These data provide evidence of the sensitivity to posture of TA H‐reflexes. As with task‐dependent changes in soleus H‐reflexes, presynaptic regulation of Ia afferent transmission is a possible mechanism. Further investigations into causes of modulation are warranted. [ABSTRACT FROM AUTHOR]

Unaccustomed eccentric exercise leads to impaired microvascular function but the underlying mechanism is unknown. In this study, we evaluated the role of oxidative stress and of nitric oxide (NO) bioavailability. Thirty young men and women performed eccentric contractions of the tibialis anterior (TA) muscle (ECC), with the contralateral leg serving as nonexercising control (CON). Participants were randomized into three groups ingesting an antioxidant cocktail (AO), beetroot juice (BR) or placebo 46 h postexercise. At baseline and 48 h postexercise, hyperemic responses to brief muscle contractions and 5 min of cuff occlusion were assessed bilaterally in the TA muscles using blood oxygen level dependent (BOLD) magnetic resonance imaging. Eccentric contractions resulted in delayed time‐to‐peak (~22%; P < 0.001), blunted peak (~21%; P < 0.001) and prolonged time‐to‐half relaxation (~12%, P < 0.001) in the BOLD response to brief contractions, with no effects of AO or BR, and no changes in CON. Postocclusive time‐to‐peak was also delayed (~54%; P < 0.001) in ECC, with no effects of AO or BR, and no changes in CON. Impaired microvascular reactivity after eccentric contractions is confined to the exercised tissue, and is not restored with acute ingestion of AO or BR. Impairments in microvascular reactivity after unaccustomed eccentric contractions may result from structural changes within the microvasculature that can diminish muscle blood flow regulation during intermittent activities requiring prompt adjustments in oxygen delivery. [ABSTRACT FROM AUTHOR]

The effects of sprint interval training (SIT) on intramyocellular (IMCL) and extramyocellular (EMCL) lipid accumulation are unclear. We tested the effects of SIT and moderate‐intensity continuous training (MICT) on IMCL and EMCL accumulation in a randomized controlled setting in two different study populations; healthy untrained men (n 28) and subjects with type 2 diabetes (T2D) or prediabetes (n 26). Proton magnetic resonance spectroscopy (1H MRS) was used to determine IMCL and EMCL in the Tibialis anterior muscle (TA) before and after a 2‐week exercise period. The exercise period comprised six sessions of SIT or MICT cycling on a cycle ergometer. IMCL increased after SIT compared to MICT (P = 0.042) in both healthy and T2D/prediabetic subjects. On EMCL the training intervention had no significant effect. In conclusion, IMCL serves as an important energy depot during exercise and can be extended by high intensity exercise. The effects of high intensity interval exercise on IMCL seem to be similar regardless of insulin sensitivity or the presence of T2D. The effects of sprint interval training (SIT) on intramyocellular (IMCL) and extramyocellular (EMCL) lipid accumulation are unclear. We showed that SIT increased intramyocellular lipids compared to Moderate‐Intensity Continuous Training in healthy men and diabetic or prediabetic subjects. [ABSTRACT FROM AUTHOR]