Synergistic Muscles Research Articles

The influence of visual information on multi-muscle control during quiet stance: a spectral analysis approach

Standing upright requires the coordination of neural drives to a large set of muscles involved in controlling human bipedal stance (i.e., postural muscles). The coordination may deteriorate in situations where standing is performed under more challenging circumstances, such as standing on a smaller base of support or not having adequate visual information. The present study investigates the role of common neural inputs in the organization of multi-muscle synergies and the effects of visual input disruption to this mechanism of control. We analyzed the strength and distribution of correlated neural inputs (measured by intermuscular coherence) to six postural muscles previously recognized as components of synergistic groups involved in the maintenance of the body's vertical positioning. Two experimental conditions were studied: quiet bipedal stance performed with opened eyes (OEs) and closed eyes (CEs). Nine participants stood quietly for 30s while the activity of the soleus, biceps femoris, lumbar erector spinae, tibialis anterior, rectus femoris, and rectus abdominis muscles were recorded using surface electrodes. Intermuscular (EMG-EMG) coherence was estimated for 12 muscle pairs formed by these muscles, including pairs formed solely by either posterior, anterior, or mixed (one posterior and one anterior) muscles. Intermuscular coherence was only found to be significant for muscle pairs formed solely by either posterior or anterior muscles, and no significant coherence was found for mixed muscle pairs. Significant intermuscular coherence was only found within a distinct frequency interval bounded between 1 and 10Hz when visual input was available (OEs trials). The strength of correlated neural inputs was similar across muscle pairs located in different joints but executing a similar function (pushing body either backward or forward) suggesting that synergistic postural groups are likely formed based on their functional role instead of their anatomical location. Absence of visual information caused a significant decrease in intermuscular coherence. These findings are consistent with the hypothesis that correlated neural inputs are a mechanism used by the CNS to assemble synergistic muscle groups. Further, this mechanism is affected by interruption of visual input.

Biceps femoris and semitendinosus—teammates or competitors? New insights into hamstring injury mechanisms in male football players: a muscle functional MRI study

BackgroundThe hamstring injury mechanism was assessed by investigating the exercise-related metabolic activity characteristics of the hamstring muscles using a muscle functional MRI (mfMRI) protocol.Methods27 healthy male football players and 27...

A differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis.

CD248 (Endosialin) is a type 1 membrane protein involved in developmental and pathological angiogenesis through its expression on pericytes and regulation of PDGFRβ signalling. Here we explore the function of CD248 in skeletal muscle angiogenesis. Two distinct forms of capillary growth (splitting and sprouting) can be induced separately by increasing microcirculatory shear stress (chronic vasodilator treatment) or by inducing functional overload (extirpation of a synergistic muscle). We show that CD248 is present on pericytes in muscle and that CD248-/- mice have a specific defect in capillary sprouting. In contrast, splitting angiogenesis is independent of CD248 expression. Endothelial cells respond to pro-sprouting angiogenic stimulus by up-regulating gene expression for HIF1α, angiopoietin 2 and its receptor TEK, PDGF-B and its receptor PDGFRβ; this response did not occur following a pro-splitting angiogenic stimulus. In wildtype mice, defective sprouting angiogenesis could be mimicked by blocking PDGFRβ signalling using the tyrosine kinase inhibitor Imatinib mesylate. We conclude that CD248 is required for PDGFRβ-dependant capillary sprouting but not splitting angiogenesis, and identify a new role for CD248 expressed on pericytes in the early stages of physiological angiogenesis during muscle remodelling.

Task constraints and minimization of muscle effort result in a small number of muscle synergies during gait.

Finding muscle activity generating a given motion is a redundant problem, since there are many more muscles than degrees of freedom. The control strategies determining muscle recruitment from a redundant set are still poorly understood. One theory of motor control suggests that motion is produced through activating a small number of muscle synergies, i.e., muscle groups that are activated in a fixed ratio by a single input signal. Because of the reduced number of input signals, synergy-based control is low dimensional. But a major criticism on the theory of synergy-based control of muscles is that muscle synergies might reflect task constraints rather than a neural control strategy. Another theory of motor control suggests that muscles are recruited by optimizing performance. Optimization of performance has been widely used to calculate muscle recruitment underlying a given motion while assuming independent recruitment of muscles. If synergies indeed determine muscle recruitment underlying a given motion, optimization approaches that do not model synergy-based control could result in muscle activations that do not show the synergistic muscle action observed through electromyography (EMG). If, however, synergistic muscle action results from performance optimization and task constraints (joint kinematics and external forces), such optimization approaches are expected to result in low-dimensional synergistic muscle activations that are similar to EMG-based synergies. We calculated muscle recruitment underlying experimentally measured gait patterns by optimizing performance assuming independent recruitment of muscles. We found that the muscle activations calculated without any reference to synergies can be accurately explained by on average four synergies. These synergies are similar to EMG-based synergies. We therefore conclude that task constraints and performance optimization explain synergistic muscle recruitment from a redundant set of muscles.

Neural and morphological adaptations of vastus lateralis and vastus medialis muscles to isokinetic eccentric training

Vastus lateralis (VL) and vastus medialis (VM) are frequently targeted in conditioning/rehabilitation programs due to their role in patellar stabilization during knee extension. This study assessed neural and muscular adaptations in these two muscles after an isokinetic eccentric training program. Twenty healthy men underwent a four-week control period followed by a 12-week period of isokinetic eccentric training. Ultrasound evaluations of VL and VM muscle thickness at rest and electromyographic evaluations during maximal isometric tests were used to assess the morphological and neural properties, respectively. No morphological and neural changes were found throughout the control period, whereas both muscles showed significant increases in thickness (VL = 6.9%; p < .001 and VM = 15.8%; p < .001) post-training. Significant increases in muscle activity were observed in VM (47.8%; p = .003), but not in VL (19.8%; p > .05) post-training. Isokinetic eccentric training produces neural and greater morphological adaptations in VM compared to VL, which shows that synergistic muscles respond differently to an eccentric isokinetic strength training program

Constitutive activation of CaMKKα signaling is sufficient but not necessary for mTORC1 activation and growth in mouse skeletal muscle.

Skeletal muscle loading/overload stimulates the Ca²⁺-activated, serine/threonine kinase Ca²⁺/calmodulin-dependent protein kinase kinase-α (CaMKKα); yet to date, no studies have examined whether CaMKKα regulates muscle growth. The purpose of this study was to determine if constitutive activation of CaMKKα signaling could stimulate muscle growth and if so whether CaMKKα is essential for this process. CaMKKα signaling was selectively activated in mouse muscle via expression of a constitutively active form of CaMKKα using in vivo electroporation. After 2 wk, constitutively active CaMKKα expression increased muscle weight (~10%) and protein content (~10%), demonstrating that activation of CaMKKα signaling can stimulate muscle growth. To determine if active CaMKKα expression stimulated muscle growth via increased mammalian target of rapamycin complex 1 (mTORC1) signaling and protein synthesis, [³H]phenylalanine incorporation into proteins was assessed with or without the mTORC1 inhibitor rapamycin. Constitutively active CaMKKα increased protein synthesis ~60%, and this increase was prevented by rapamycin, demonstrating a critical role for mTORC1 in this process. To determine if CaMKKα is essential for growth, muscles from CaMKKα knockout mice were stimulated to hypertrophy via unilateral ablation of synergist muscles (overload). Surprisingly, compared with wild-type mice, muscles from CaMKKα knockout mice exhibited greater growth (~15%) and phosphorylation of the mTORC1 substrate 70-kDa ribosomal protein S6 kinase (Thr³⁸⁹; ~50%), demonstrating that CaMKKα is not essential for overload-induced mTORC1 activation or muscle growth. Collectively, these results demonstrate that activation of CaMKKα signaling is sufficient but not necessary for activation of mTORC1 signaling and growth in mouse skeletal muscle.

Vestibulocollic reflexes in the absence of head postural control.

Percutaneous electrical vestibular stimulation evokes reflexive responses in appendicular muscles that are suppressed during tasks in which the muscles are not contributing to balance control. In neck muscles, which stabilize the head on the torso and in space, it is unclear whether similar postural task dependence shapes vestibular reflexes. We investigated whether vestibulocollic reflexes are modulated during tasks in which vestibular information is not directly relevant to maintaining the head balanced on the torso. We hypothesized that vestibulocollic reflexes would be 1) evoked when neck muscles are not involved in balancing the head on the torso and 2) invariant across synergistic neck muscle contraction tasks. Muscle activity was recorded bilaterally in sternocleidomastoid and splenius capitis muscles during head-free and head-fixed conditions while subjects were exposed to stochastic electrical vestibular stimulation (± 5 mA, 0-75 Hz). Significant vestibular reflex responses (P < 0.05) were observed during head-free and head-fixed trials. Response magnitude and timing were similar between head-free and head-fixed trials for sternocleidomastoid, but splenius capitis magnitudes decreased with the head fixed by ∼ 25% (P < 0.05). Nevertheless, this indicates that vestibulocollic responses are evoked independent of the requirement to maintain postural control of the head on the torso. Response magnitude and timing were similar across focal muscle contractions (i.e., axial rotation/flexion/extension) provided the muscle was active. In contrast, when subjects cocontracted neck muscles, vestibular-evoked responses decreased in sternocleidomastoid by ∼ 30-45% (P < 0.05) compared with focal muscle contractions but remained unchanged in splenius capitis. These results indicate robust vestibulocollic reflex coupling, which we suggest functions through its closed-loop influence on head posture to ensure cervical spine stabilization.

Operant conditioning of the soleus H-reflex does not induce long-term changes in the gastrocnemius H-reflexes and does not disturb normal locomotion in humans.

In normal animals, operant conditioning of the spinal stretch reflex or the H-reflex has lesser effects on synergist muscle reflexes. In rats and people with incomplete spinal cord injury (SCI), soleus H-reflex operant conditioning can improve locomotion. We studied in normal humans the impact of soleus H-reflex down-conditioning on medial (MG) and lateral gastrocnemius (LG) H-reflexes and on locomotion. Subjects completed 6 baseline and 30 conditioning sessions. During conditioning trials, the subject was encouraged to decrease soleus H-reflex size with the aid of visual feedback. Every sixth session, MG and LG H-reflexes were measured. Locomotion was assessed before and after conditioning. In successfully conditioned subjects, the soleus H-reflex decreased 27.2%. This was the sum of within-session (task dependent) adaptation (13.2%) and across-session (long term) change (14%). The MG H-reflex decreased 14.5%, due mainly to task-dependent adaptation (13.4%). The LG H-reflex showed no task-dependent adaptation or long-term change. No consistent changes were detected across subjects in locomotor H-reflexes, EMG activity, joint angles, or step symmetry. Thus, in normal humans, soleus H-reflex down-conditioning does not induce long-term changes in MG/LG H-reflexes and does not change locomotion. In these subjects, task-dependent adaptation of the soleus H-reflex is greater than it is in people with SCI, whereas long-term change is less. This difference from results in people with SCI is consistent with the fact that long-term change is beneficial in people with SCI, since it improves locomotion. In contrast, in normal subjects, long-term change is not beneficial and may necessitate compensatory plasticity to preserve satisfactory locomotion.

Immediate effects and short-term retention of multi-modal instruction compared to written only on muscle activity during the prone horizontal abduction exercise in individuals with shoulder pain

In rehabilitation, exercise instructions are multi-modal and can include a focus of increasing mean activity of a target muscle and inhibiting aberrant synergistic muscle activity, particularly during shoulder exercises, such as the prone horizontal abduction (PHA). The objective was to compare the immediate effects and short-term retention of multi-modal exercise instruction by a physical therapist written only instruction on normalized mean upper and lower trapezius muscle activity during three phases (concentric/isometric/eccentric) versus of an isotonic PHA exercise between participants with and without shoulder pain. Surface electromyography (EMG) was recorded from fourteen healthy participants and twelve participants with shoulder pain during the PHA exercise under two conditions: (1) written only instructions and (2) multi-modal instruction. Retention of multi-modal instruction on muscle activity was assessed one week later. Results demonstrate 12.8–16.0% increase in lower trapezius muscle activity during the concentric and isometric phases with multi-modal instructions in both groups. Inhibition of the upper trapezius did not occur in either group. Facilitation effects were maintained in short-term follow-up. Findings suggest that regardless of shoulder pain, multi-modal instruction by a physical therapist facilitates greater neuromuscular activity of a targeted muscle compared to written instructions alone and these effects are retained.

Motor modules of human locomotion: influence of EMG averaging, concatenation, and number of step cycles.

Locomotion can be investigated by factorization of electromyographic (EMG) signals, e.g., with non-negative matrix factorization (NMF). This approach is a convenient concise representation of muscle activities as distributed in motor modules, activated in specific gait phases. For applying NMF, the EMG signals are analyzed either as single trials, or as averaged EMG, or as concatenated EMG (data structure). The aim of this study is to investigate the influence of the data structure on the extracted motor modules. Twelve healthy men walked at their preferred speed on a treadmill while surface EMG signals were recorded for 60s from 10 lower limb muscles. Motor modules representing relative weightings of synergistic muscle activations were extracted by NMF from 40 step cycles separately (EMGSNG), from averaging 2, 3, 5, 10, 20, and 40 consecutive cycles (EMGAVR), and from the concatenation of the same sets of consecutive cycles (EMGCNC). Five motor modules were sufficient to reconstruct the original EMG datasets (reconstruction quality >90%), regardless of the type of data structure used. However, EMGCNC was associated with a slightly reduced reconstruction quality with respect to EMGAVR. Most motor modules were similar when extracted from different data structures (similarity >0.85). However, the quality of the reconstructed 40-step EMGCNC datasets when using the muscle weightings from EMGAVR was low (reconstruction quality ~40%). On the other hand, the use of weightings from EMGCNC for reconstructing this long period of locomotion provided higher quality, especially using 20 concatenated steps (reconstruction quality ~80%). Although EMGSNG and EMGAVR showed a higher reconstruction quality for short signal intervals, these data structures did not account for step-to-step variability. The results of this study provide practical guidelines on the methodological aspects of synergistic muscle activation extraction from EMG during locomotion.

Motor Variability during Sustained Contractions Increases with Cognitive Demand in Older Adults.

To expose cortical involvement in age-related changes in motor performance, we compared steadiness (force fluctuations) and fatigability of submaximal isometric contractions with the ankle dorsiflexor muscles in older and young adults and with varying levels of cognitive demand imposed. Sixteen young (20.4 ± 2.1 year: 8 men, 9 women) and 17 older adults (68.8 ± 4.4 years: 9 men, 8 women) attended three sessions and performed a 40 s isometric contraction at 5% maximal voluntary contraction (MVC) force followed by an isometric contraction at 30% MVC until task failure. The cognitive demand required during the submaximal contractions in each session differed as follows: (1) high-cognitive demand session where difficult mental math was imposed (counting backward by 13 from a 4-digit number); (2) low-cognitive demand session which involved simple mental math (counting backward by 1); and (3) control session with no mental math. Anxiety was elevated during the high-cognitive demand session compared with other sessions for both age groups but more so for the older adults than young adults (p < 0.05). Older adults had larger force fluctuations than young adults during: (1) the 5% MVC task as cognitive demand increased (p = 0.007), and (2) the fatiguing contraction for all sessions (p = 0.002). Time to task failure did not differ between sessions or age groups (p > 0.05), but the variability between sessions (standard deviation of three sessions) was greater for older adults than young (2.02 ± 1.05 vs. 1.25 ± 0.51 min, p < 0.05). Thus, variability in lower limb motor performance for low- and moderate-force isometric tasks increased with age and was exacerbated when cognitive demand was imposed, and may be related to modulation of synergist and antagonist muscles and an altered neural strategy with age originating from central sources. These data have significant implications for cognitively demanding low-force motor tasks that are relevant to functional and ergonomic in an aging workforce.

Is spinal excitability of the triceps surae mainly affected by muscle activity or body position?

The aim of this study was to determine how muscle activity and body orientation contribute to the triceps surae spinal transmission modulation, when moving from a sitting to a standing position. Maximal Hoffmann-reflex (Hmax) and motor potential (Mmax) were evoked in the soleus (SOL), medial and lateral gastrocnemius in 10 male subjects and in three conditions, passive sitting, active sitting and upright standing, with the same SOL activity in active sitting and upright standing. Moreover volitional wave (V) was evoked in the two active conditions (i.e., active sitting and upright standing). The results showed that SOL Hmax/Mmax was lower in active sitting than in passive sitting, while for the gastrocnemii it was not significantly altered. For the three plantar flexors, Hmax/Mmax was lower in upright standing than in active sitting, whereas V/Mmax was not modulated. SOL H-reflex is therefore affected by the increase in muscle activity and change in body orientation, while, in the gastrocnemii, it was only affected by a change in posture. In conclusion, passing from a sitting to a standing position affects the Hmax/Mmax of the whole triceps surae, but the mechanisms responsible for this change differ among the synergist muscles. The V/Mmax does not change when upright stance is assumed. This means that the increased inhibitory activity in orthostatic position is compensated by an increased excitatory inflow to the α-motoneurons of central and/or peripheral origin.

Plantarflexor muscle function in healthy and chronic Achilles tendon pain subjects evaluated by the use of EMG and PET imaging

BackgroundAchilles tendon pathologies may alter the coordinative strategies of synergistic calf muscles. We hypothesized that both surface electromyography and positron emission tomography would reveal differences between symptomatic and asymptomatic legs in Achilles tendinopathy patients and between healthy controls. MethodsEleven subjects with unilateral chronic Achilles tendon pain (28years) and eleven matched controls (28years) were studied for triceps surae and flexor hallucis longus muscle activity in response to repetitive isometric plantarflexion tasks performed at 30% of maximal voluntary contraction using surface electromyography and glucose uptake using positron emission tomography. Additionally, Achilles tendon glucose uptake was quantified. FindingsNormalized myoelectric activity of soleus was higher (P<0.05) in the symptomatic leg versus the contralateral and control legs despite lower absolute force level maintained (P<0.005). Electromyography amplitude of flexor hallucis longus was also greater on the symptomatic side compared to the healthy leg (P<0.05). Both the symptomatic and asymptomatic legs tended to have higher glucose uptake compared to the control legs (overall effect size: 0.9 and 1.3, respectively). Achilles tendon glucose uptake was greater in both legs of the patient group (P<0.05) compared to controls. Maximal plantarflexion force was ~14% greater in the healthier leg compared to the injured leg in the patient group. InterpretationsWhile the electromyography showed greater relative amplitude in the symptomatic leg, the results based on muscle glucose uptake suggested relatively similar behavior of both legs in the patient group. Higher glucose uptake in the symptomatic Achilles tendon suggests a higher metabolic demand.

Is A New Combination of Tendon Transfers For Radial Nerve Palsy (RNP) Needed?

Radial nerve palsy following traumatic humeral diaphyseal fractures occurs uncommonly. Most recover with good outcome. However the cases with poor outcome or recovery will have tendon transfers to regain the lost functions. Various tendon transfer methods and choices are available in literatures citing acceptable to good results. We report a case of radial nerve transection secondary to a closed traumatic diaphyseal fracture of the humerus which did not improve despite the repair. As many conventional technique produce asynergistic muscle action with secondary post-transfer deformity, thus we had resorted to tendon transfer procedure using an unconventional donor and recipient tendons yielding good results. This new combination of tendon transfers was invented involves better dynamic correlation of synergistic muscles action and produces good outcome and hand function. Tendons transfer, radial nerve palsy.

Age-Related Weakness of Proximal Muscle Studied with Motor Cortical Mapping: A TMS Study

Aging-related weakness is due in part to degeneration within the central nervous system. However, it is unknown how changes to the representation of corticospinal output in the primary motor cortex (M1) relate to such weakness. Transcranial magnetic stimulation (TMS) is a noninvasive method of cortical stimulation that can map representation of corticospinal output devoted to a muscle. Using TMS, we examined age-related alterations in maps devoted to biceps brachii muscle to determine whether they predicted its age-induced weakness. Forty-seven right-handed subjects participated: 20 young (22.6±0.90 years) and 27 old (74.96±1.35 years). We measured strength as force of elbow flexion and electromyographic activation of biceps brachii during maximum voluntary contraction. Mapping variables included: 1) center of gravity or weighted mean location of corticospinal output, 2) size of map, 3) volume or excitation of corticospinal output, and 4) response density or corticospinal excitation per unit area. Center of gravity was more anterior in old than in young (p<0.001), though there was no significant difference in strength between the age groups. Map size, volume, and response density showed no significant difference between groups. Regardless of age, center of gravity significantly predicted strength (β = −0.34, p = 0.005), while volume adjacent to the core of map predicted voluntary activation of biceps (β = 0.32, p = 0.008). Overall, the anterior shift of the map in older adults may reflect an adaptive change that allowed for the maintenance of strength. Laterally located center of gravity and higher excitation in the region adjacent to the core in weaker individuals could reflect compensatory recruitment of synergistic muscles. Thus, our study substantiates the role of M1 in adapting to aging-related weakness and subtending strength and muscle activation across age groups. Mapping from M1 may offer foundation for an examination of mechanisms that preserve strength in elderly.

Anodal Transcranial Direct Current Stimulation Alters Elbow Flexor Muscle Recruitment Strategies

Transcranial direct current stimulation (tDCS) is known to reliably alter motor cortical excitability in a polarity dependent fashion such that anodal stimulation increases cortical excitability and cathodal stimulation inhibits cortical excitability. However, the effect of tDCS on agonist and antagonist volitional muscle activation is currently not known. This study investigated the effect of motor cortical anodal tDCS on EMG/force relationships of biceps brachii (agonist) and triceps brachii (antagonist) using surface electromyography (EMG). Eighteen neurologically intact adults (9 tDCS and 9 controls) participated in this study. EMG/force relationships were established by having subjects perform submaximal isometric contractions at several force levels (12.5%, 25%, 37.5%, and 50% of maximum). Results showed that anodal tDCS significantly affected the EMG/force relationship of the biceps brachii muscle. Specifically, anodal tDCS increased the magnitude of biceps brachii activation at 37.5% and 50% of maximum. Anodal tDCS also resulted in an increase in the peak force and EMG values during maximal contractions as compared to the control condition. EMG analyses of other elbow muscles indicated that the increase in biceps brachii activation after anodal tDCS was not related to alterations in synergistic or antagonistic muscle activity. Our results indicate that anodal tDCS significantly affects the voluntary EMG/force relationship of the agonist muscles without altering the coactivation of the antagonistic muscles. The most likely explanation for the observed greater EMG per unit force after anodal tDCS appears to be related to alterations in motor unit recruitment strategies.

Intrinsic transient tracheal occlusion training and myogenic remodeling of rodent parasternal intercostal fibers.

It is recognized that diaphragm muscle plasticity occurs with mechanical overloads, yet less is known about synergistic parasternal intercostal muscle fiber remodeling. We conducted overload training with intrinsic transient tracheal occlusion (ITTO) exercises in conscious animals. We hypothesized that ITTO would yield significant fiber hypertrophy and myogenic activation that would parallel diaphragm fiber remodeling. Sprague-Dawley rats underwent placement of a tracheal cuff and were randomly assigned to receive daily 10 min sessions of conscious ITTO or observation (sham) over 2 wk. After training, fiber morphology, myosin heavy chain (MHC) isoform composition, cross-sectional area, proportion of Pax7-positive nuclei, and presence of embryonic MHC (eMHC) were quantified. Type IIx/b fibers were 20% larger after ITTO training than with sham training (ITTO: 4,431 +/– 676 μm2, sham: 3,689 +/– 400 μm2, p < 0.05), and type I fibers were more prevalent after ITTO (p < 0.01). Expression of Pax7 was increased in ITTO parasternals and diaphragm (p < 0.05). In contrast, the proportion of eMHC-positive fibers was increased only in ITTO parasternals (1.2% [3.4%–0.6%], sham: 0% [0.6%–0%], p < 0.05). Although diaphragm and parasternal type II fibers hypertrophy to a similar degree, myogenic remodeling appears to differ between the two muscles.

Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy

extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown. in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus). following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis. taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.

Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy

extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown. in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus). following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis. taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.

Reduced Renshaw recurrent inhibition after neonatal sciatic nerve crush in rats.

Renshaw recurrent inhibition (RI) plays an important gated role in spinal motion circuit. Peripheral nerve injury is a common disease in clinic. Our current research was designed to investigate the change of the recurrent inhibitory function in the spinal cord after the peripheral nerve crush injury in neonatal rat. Sciatic nerve crush was performed on 5-day-old rat puppies and the recurrent inhibition between lateral gastrocnemius-soleus (LG-S) and medial gastrocnemius (MG) motor pools was assessed by conditioning monosynaptic reflexes (MSR) elicited from the sectioned dorsal roots and recorded either from the LG-S and MG nerves by antidromic stimulation of the synergist muscle nerve. Our results demonstrated that the MSR recorded from both LG-S or MG nerves had larger amplitude and longer latency after neonatal sciatic nerve crush. The RI in both LG-S and MG motoneuron pools was significantly reduced to virtual loss (15–20% of the normal RI size) even after a long recovery period upto 30 weeks after nerve crush. Further, the degree of the RI reduction after tibial nerve crush was much less than that after sciatic nerve crush indicatig that the neuron-muscle disconnection time is vital to the recovery of the spinal neuronal circuit function during reinnervation. In addition, sciatic nerve crush injury did not cause any spinal motor neuron loss but severally damaged peripheral muscle structure and function. In conclusion, our results suggest that peripheral nerve injury during neonatal early development period would cause a more sever spinal cord inhibitory circuit damage, particularly to the Renshaw recurrent inhibition pathway, which might be the target of neuroregeneration therapy.