The MuSK-BMP pathway maintains myofiber size in slow muscle through regulation of Akt-mTOR signaling.

Myofiber size regulation is critical in health, disease, and aging. MuSK (muscle-specific kinase) is a BMP (bone morphogenetic protein) co-receptor that promotes and shapes BMP signaling. MuSK is expressed at all neuromuscular junctions and is also present extrasynaptically in the mouse soleus, whose predominantly oxidative fiber composition is akin to that of human muscle. To investigate the role of the MuSK-BMP pathway in vivo, we generated mice lacking the BMP-binding MuSK Ig3 domain. These ∆Ig3-MuSK mice are viable and fertile with innervation levels comparable to wild type. In 3-month-old mice, myofibers are smaller in the slow soleus, but not in the fast tibialis anterior (TA). Transcriptomic analysis revealed soleus-selective decreases in RNA metabolism and protein synthesis pathways as well as dysregulation of IGF1-Akt-mTOR pathway components. Biochemical analysis showed that Akt-mTOR signaling is reduced in soleus but not TA. We propose that the MuSK-BMP pathway acts extrasynaptically to maintain myofiber size in slow muscle by promoting protein synthetic pathways including IGF1-Akt-mTOR signaling. These results reveal a novel mechanism for regulating myofiber size in slow muscle and introduce the MuSK-BMP pathway as a target for promoting muscle growth and combatting atrophy.

Need for speed: Human fast-twitch mitochondria favor power over efficiency.

OBJECTIVE: Human skeletal muscle consists of a mixture of slow- and fast-twitch fibers with distinct capacities for contraction mechanics, fermentation, and oxidative phosphorylation. While the divergence in mitochondrial volume favoring slow-twitch fibers is well established, data on the fiber type-specific intrinsic mitochondrial function and morphology are highly limited with existing data mainly being generated in animal models. This highlights the need for more human data on the topic. METHODS: Here, we utilized THRIFTY, a rapid fiber type identification protocol to detect, sort, and pool fast- and slow-twitch fibers within 6 h of muscle biopsy sampling. Respiration of permeabilized fast- and slow-twitch fiber pools was then analyzed with high-resolution respirometry. Using standardized western blot procedures, muscle fiber pools were subsequently analyzed for control proteins and key proteins related to respiratory capacity. RESULTS: Maximal complex I+II respiration was 25% higher in human slow-twitch fibers compared to fast-twitch fibers. However, per mitochondrial volume, the respiratory rate of mitochondria in fast-twitch fibers was approximately 50% higher for complex I+II, which was primarily mediated through elevated complex II respiration. Furthermore, the abundance of complex II protein and proteins regulating cristae structure were disproportionally elevated in mitochondria of the fast-twitch fibers. The difference in intrinsic respiratory rate was not reflected in fatty acid-or complex I respiration. CONCLUSION: Mitochondria of human fast-twitch muscle fibers compensate for their lack of volume by substantially elevating intrinsic respiratory rate through increased reliance on complex II.

Molecular mechanisms underlying the impact of muscle fiber types on meat quality in livestock and poultry.

In the past, the primary emphasis of livestock and poultry breeding was mainly on improving the growth rate, meat production efficiency and disease resistance. However, the improvement of meat quality has become a major industrial focus due to the ongoing advancements in livestock and poultry breeding. Skeletal muscles consist of multinucleated myofibers formed through the processes of myoblast proliferation, differentiation and fusion. Muscle fibers can be broadly classified into two main types: slow-twitch (Type I) and fast-twitch (Type II). Fast-twitch fibers can be further categorized into Type IIa, Type IIx, and Type IIb. The proportion of Type I and Type IIa muscle fibers is positively associated with meat quality, while the presence of Type IIb muscle fibers in skeletal muscle tissue is inversely related to meat quality. Consequently, muscle fiber composition directly influences meat quality. The distribution of these fiber types within skeletal muscle is governed by a complex network, which encompasses numerous pivotal regulators and intricate signaling pathways. This article aims to succinctly outline the parameters utilized for assessing meat quality, elucidate the relationship between muscle fiber composition and meat quality as well as elaborate on the relevant genetic factors and their molecular mechanisms that regulate muscle fiber types in livestock and poultry. This summary will enrich our comprehension of how to improve meat quality in livestock and poultry, providing valuable insights for future improvements.

An Early and Sustained Inflammatory State Induces Muscle Changes and Establishes Obesogenic Characteristics in Wistar Rats Exposed to the MSG-Induced Obesity Model.

The model of obesity induced by monosodium glutamate cytotoxicity on the hypothalamic nuclei is widely used in the literature. However, MSG promotes persistent muscle changes and there is a significant lack of studies that seek to elucidate the mechanisms by which damage refractory to reversal is established. This study aimed to investigate the early and chronic effects of MSG induction of obesity upon systemic and muscular parameters of Wistar rats. The animals were exposed to MSG subcutaneously (4 mg·g-1 b.w.) or saline (1.25 mg·g-1 b.w.) daily from PND01 to PND05 (n = 24). Afterwards, in PND15, 12 animals were euthanized to determine the plasma and inflammatory profile and to assess muscle damage. In PND142, the remaining animals were euthanized, and samples for histological and biochemical analyses were obtained. Our results suggest that early exposure to MSG reduced growth, increased adiposity, and inducted hyperinsulinemia and a pro-inflammatory scenario. In adulthood, the following were observed: peripheral insulin resistance, increased fibrosis, oxidative distress, and a reduction in muscle mass, oxidative capacity, and neuromuscular junctions, increased fibrosis, and oxidative distress. Thus, we can conclude that the condition found in adult life and the difficulty restoring in the muscle profile is related to the metabolic damage established early on.

Influence of Dietary Protein Source and Level on Histological Properties of Muscle and Adipose Tissue of Lambs.

The muscle and adipose tissue histological properties in wether and ewe lambs of Gentile di Puglia breed, fed diets including two protein sources [soybean meal (SB) and SB plus distillers dried grain with solubles (DD)] and three protein levels (12.5, 15.7, and 18.9%) were evaluated. Muscle samples were collected from the longissimus/rump, cut, and stained (reciprocal aerobic and anaerobic stains) for muscle fiber typing and fat cell characterization. Fibers were classified as α-red, ß-red, and α-white. Lambs fed SB had larger α-white (p < 0.10) and smaller-diameter ß-red and α-red fibers (p < 0.05). Among dietary protein levels, lambs fed 12.5% protein exhibited the highest percentage of α-red and the greatest diameter of α-white fibers, whereas wethers had a higher percentage of α-red (p < 0.05), and ewes had a higher percentage of α-white fibers (p < 0.05). Intramuscular fat cells were larger (p < 0.10) in ewes than in wethers. Lambs in the group fed 12.5% protein had larger subcutaneous fat cells at the sacral vertebrae location. Overall, both sources and levels of dietary protein had significant effects on lamb muscle and fat histological features, suggesting the potential of modulating muscle or fiber types through dietary protein strategies.

Morphological and histochemical characterization of the pectoral fin muscle of batoids.

Batoids differ from other elasmobranch fishes in that they possess dorsoventrally flattened bodies with enlarged muscled pectoral fins. Most batoids also swim using either of two modes of locomotion: undulation or oscillation of the pectoral fins. In other elasmobranchs (e.g., sharks), the main locomotory muscle is located in the axial myotome; in contrast, the main locomotory muscle in batoids is found in the enlarged pectoral fins. The pectoral fin muscles of sharks have a simple structure, confined to the base of the fin; however, little to no data are available on the more complex musculature within the pectoral fins of batoids. Understanding the types of fibers and their arrangement within the pectoral fins may elucidate how batoid fishes are able to utilize such unique swimming modes. In the present study, histochemical methods including succinate dehydrogenase (SDH) and immunofluoresence were used to determine the different fiber types comprising these muscles in three batoid species: Atlantic stingray (Dasyatis sabina), ocellate river stingray (Potamotrygon motoro) and cownose ray (Rhinoptera bonasus). All three species had muscles comprised of two muscle fiber types (slow-red and fast-white). The undulatory species, D. sabina and P. motoro, had a larger proportion of fast-white muscle fibers compared to the oscillatory species, R. bonasus. The muscle fiber sizes were similar between each species, though generally smaller compared to the axial musculature in other elasmobranch fishes. These results suggest that batoid locomotion can be distinguished using muscle fiber type proportions. Undulatory species are more benthic with fast-white fibers allowing them to contract their muscles quickly, as a possible means of escape from potential predators. Oscillatory species are pelagic and are known to migrate long distances with muscles using slow-red fibers to aid in sustained swimming.

Tipos de fibras de los músculos intrínsecos laríngeos de seres humanos: una revisión de la literatura / Fiber types in human intrinsic laryngeal muscles: a literature review

El estudio de las fibras musculares permite comprender con mejor detalle la composición de los músculos y sus características funcionales. Además, facilita la aplicación de programas de entrenamiento y rehabilitación basados en las vías energéticas que regulan la contracción muscular. Su estudio generalmente va unido al análisis de las cadenas pesadas de miosina (MyHC), las que informan sobre las características y propiedades funcionales del músculo. El objetivo de este trabajo fue sintetizar la evidencia científica disponible sobre la distribución de fibras musculares y de isoformas de cadenas pesadas de miosina de los músculos intrínsecos de la laringe de seres humanos. Se realizó una revisión sistemática de la literatura mediante el análisis de artículos encontrados en las bases de datos PubMed, EBSCOHost y SciELO. Los hallazgos informan sobre la existencia de fibras tónicas lentas y tipo I, II, IIA y IIX/IIB. Además, se reconoce la presencia de las isoformas MyHC-I, MyHC-IIA, MyHC-IIX, MyHC-Fetal, MyHC-L y MyHC-IIB. En conclusión, los músculos intrínsecos de la laringe presentan una mezcla de fibras y de isoformas de MyHC lentas y rápidas,la que obedece a adaptaciones y cambios evolutivos que han permitido, por ejemplo, las características fonatorias que presenta la voz del ser humano.

The study of muscle fibers allows the composition of muscles and their functional characteristics to be understood in greaterdetail. In addition, it makes it possible to applytraining and rehabilitation programs based on the energypathways that regulatemuscle contraction. Studying muscle fibers is generally associated withthe analysis of myosin heavy chains (MHC) which provide information on the functional characteristics and properties of muscles. The objective of this study was to synthesize the available scientific evidence onthe distribution of muscle fibers and myosin heavy chain isoforms present in the intrinsic laryngeal muscles of human beings. A systematic reviewof the literature was carried outand articles found on PubMed, EBSCOHost,and SciELOwere analyzed.The findings showthe presenceof slow-tonic, type I, type II, type IIA, and type IIX/IIB fibers. Additionally,isoforms MHC-I, MHC-IIA, MHC-IIX, MHC-Fetal, MHC-L, and MHC-IIB canbe found. In conclusion, intrinsic laryngeal muscles are composed ofa combination of slow and fast fibers and MHC isoforms, derived from evolutionary adaptations and changes which have given way, among other things, to the phonetic characteristics ofthe human voice.

Sox6 Differentially Regulates Inherited Myogenic Abilities and Muscle Fiber Types of Satellite Cells Derived from Fast- and Slow-Type Muscles.

Adult skeletal muscle is primarily divided into fast and slow-type muscles, which have distinct capacities for regeneration, metabolism and contractibility. Satellite cells plays an important role in adult skeletal muscle. However, the underlying mechanisms of satellite cell myogenesis are poorly understood. We previously found that Sox6 was highly expressed in adult fast-type muscle. Therefore, we aimed to validate the satellite cell myogenesis from different muscle fiber types and investigate the regulation of Sox6 on satellite cell myogenesis. First, we isolated satellite cells from fast- and slow-type muscles individually. We found that satellite cells derived from different muscle fiber types generated myotubes similar to their origin types. Further, we observed that cells derived from fast muscles had a higher efficiency to proliferate but lower potential to self-renew compared to the cells derived from slow muscles. Then we demonstrated that Sox6 facilitated the development of satellite cells-derived myotubes toward their inherent muscle fiber types. We revealed that higher expression of Nfix during the differentiation of fast-type muscle-derived myogenic cells inhibited the transcription of slow-type isoforms (MyH7B, Tnnc1) by binding to Sox6. On the other hand, Sox6 activated Mef2C to promote the slow fiber formation in slow-type muscle-derived myogenic cells with Nfix low expression, showing a different effect of Sox6 on the regulation of satellite cell development. Our findings demonstrated that satellite cells, the myogenic progenitor cells, tend to develop towards the fiber type similar to where they originated. The expression of Sox6 and Nfix partially explain the developmental differences of myogenic cells derived from fast- and slow-type muscles.

Immunohistochemistry of kangaroo rat hindlimb muscles.

Kangaroo rats (Dipodomys spp.) use specialized bipedal hopping like that of kangaroos. In contrast to kangaroos that have elastic tendons capable of storing energy, kangaroo rats have inelastic tendons that are unable to store large amounts of energy. Thus, the musculature of the ankle joint provides the greatest power contribution to kangaroo rat hopping. Skeletal muscle can be characterized by several fiber types, including slow twitch (Type I) and fast twitch (Type II) fibers. Fast fibers are found in higher concentration in muscles that perform quick, dynamic movements, whereas slow fibers are found in higher proportion in muscles that perform slow, endurant movements. Using fiber type specific antibodies, we identified four pure (Types I, IIA, IIB, and IIX) and two hybrid (Types I/IIA and IIA/IIX) fiber types in six hindlimb muscles from three kangaroo rats (Dipodomys merriami) to investigate the relationship between fiber composition and hindlimb muscle function. Hindlimb muscles (except soleus) were dominated by Type IIB fibers, which were largest in cross-sectional area, and are known to be best suited for rapid and explosive movements. Oxidative Type IIA and Type IIX fibers were found at moderate concentrations and likely function in maintaining continual saltatory locomotion. Thus, kangaroo rats can use these two fiber type populations as "gears" for both endurant and explosive behaviors.

Phosphoproteomic analysis identifies differentially expressed phosphorylation sites that affect muscle fiber type in pigs.

Skeletal muscle of livestock is composed of both fast- and slow-twitch muscle fibers, which are key factors in their meat quality. However, the role of protein phosphorylation in muscle fiber type is not completely understood. Here, a fast-twitch (biceps femoris, BF) and slow-twitch (soleus, SOL) muscle tissue sample was collected from three male offspring of Duroc and Meishan pigs. We demonstrate that the meat quality of SOL muscle is significantly better than that of BF muscle. We further used phosphoproteomic profiling of BF and SOL muscles to identify differences between these muscle types. A total of 2,327 phosphorylation sites from 770 phosphoproteins were identified. Among these sites, 287 differentially expressed phosphorylation sites (DEPSs) were identified between BF and SOL. GO and KEGG enrichment analysis of proteins containing DEPSs showed that these phosphorylated proteins were enriched in the glycolytic process GO term and the AMPK signaling pathway. A protein-protein interaction (PPI) analysis reveals that these phosphorylated proteins interact with each other to regulate the transformation of muscle fiber type. These analyses reveal that protein phosphorylation modifications are involved in porcine skeletal muscle fiber type transformation. This study provides new insights into the molecular mechanisms by which protein phosphorylation regulates muscle fiber type transformation and meat quality in pigs.

Skeletal muscle phenotype and game performance in elite women football players.

We combined game activity analyses with skeletal muscle phenotypes and comprehensive physiological testing to elucidate factors of importance for physical performance in elite women's football. GPS-data from an experimental game, sprint and endurance testing, and muscle tissue analysis of metabolic enzyme activity, protein expression and fiber type composition were completed for international top-level women players (n = 20; age; 23 ± 4 yrs, height; 166 ± 10 cm, weight; 60 ± 8 kg; VO2max ; 51 ± 6 ml/min/kg). Muscle monocarboxylate transporter 4 (MCT4) protein expression explained 46% of the variance in total game distance, while the ability to maintain high-intensity running (HIR) during the final 15 min of the game correlated to myosin heavy chain 1 (MHCI) and Na+ -K+ ATPase ß1, FXYD1 (phospholemman) and superoxide dismutase 2 (SOD2) protein expression (range: r = 0.51-0.71; all p < 0.05). Total HIR distance correlated with (MHCIIa) protein expression (r = 0.51; p < 0.05), while muscle Na+ /H+ exchanger 1 (NHE1) protein explained 36% of the variance in game sprint distance (p < 0.05). Total game accelerations (actions >4 m/s2 ) correlated with platelet endothelial cell adhesion molecule (PECAM-1) protein expression (r = 0.51; p < 0.05), while concentric knee flexor strength explained 42-62% of the variance in intense decelerations (>4 m/s2 ). In conclusion, for elite women players' game endurance performance and resistance to end-game fatigue were affected by monocarboxylate transporter expression and myosin heavy chain profile. HIR was also correlated to ion transporter expression and muscle antioxidative capacity. Finally, the importance of functional strength and measures of muscle vascularization in relation to total game decelerations and accelerations, respectively, illustrates the complex physiological demands in elite women's football.

Protein profile of fiber types in human skeletal muscle: a single-fiber proteomics study.

BACKGROUND: Human skeletal muscle is composed of three major fiber types, referred to as type 1, 2A, and 2X fibers. This heterogeneous cellular composition complicates the interpretation of studies based on whole skeletal muscle lysate. A single-fiber proteomics approach is required to obtain a fiber-type resolved quantitative information on skeletal muscle pathophysiology. METHODS: Single fibers were dissected from vastus lateralis muscle biopsies of young adult males and processed for mass spectrometry-based single-fiber proteomics. We provide and analyze a resource dataset based on relatively pure fibers, containing at least 80% of either MYH7 (marker of slow type 1 fibers), MYH2 (marker of fast 2A fibers), or MYH1 (marker of fast 2X fibers). RESULTS: In a dataset of more than 3800 proteins detected by single-fiber proteomics, we selected 404 proteins showing a statistically significant difference among fiber types. We identified numerous type 1 or 2X fiber type-specific protein markers, defined as proteins present at 3-fold or higher levels in these compared to other fiber types. In contrast, we could detect only two 2A-specific protein markers in addition to MYH2. We observed three other major patterns: proteins showing a differential distribution according to the sequence 1 > 2A > 2X or 2X > 2A > 1 and type 2-specific proteins expressed in 2A and 2X fibers at levels 3 times greater than in type 1 fibers. In addition to precisely quantifying known fiber type-specific protein patterns, our study revealed several novel features of fiber type specificity, including the selective enrichment of components of the dystrophin and integrin complexes, as well as microtubular proteins, in type 2X fibers. The fiber type-specific distribution of some selected proteins revealed by proteomics was validated by immunofluorescence analyses with specific antibodies. CONCLUSION: We here show that numerous muscle proteins, including proteins whose function is unknown, are selectively enriched in specific fiber types, pointing to potential implications in muscle pathophysiology. This reinforces the notion that single-fiber proteomics, together with recently developed approaches to single-cell proteomics, will be instrumental to explore and quantify muscle cell heterogeneity.

Biological Determinants of Track and Field Throwing Performance.

Track and field throwing performance is determined by a number of biomechanical and biological factors which are affected by long-term training. Although much of the research has focused on the role of biomechanical factors on track and field throwing performance, only a small body of scientific literature has focused on the connection of biological factors with competitive track and field throwing performance. The aim of this review was to accumulate and present the current literature connecting the performance in track and field throwing events with specific biological factors, including the anthropometric characteristics, the body composition, the neural activation, the fiber type composition and the muscle architecture characteristics. While there is little published information to develop statistical results, the results from the current review suggest that major biological determinants of track and field throwing performance are the size of lean body mass, the neural activation of the protagonist muscles during the throw and the percentage of type II muscle fiber cross-sectional area. Long-term training may enhance these biological factors and possibly lead to a higher track and field throwing performance. Consequently, coaches and athletes should aim at monitoring and enhancing these parameters in order to increase track and field throwing performance.

Hoxa11 and Hoxa13 facilitate slow-twitch muscle formation in C2C12 cells and indirectly affect the lipid deposition of 3T3-L1 cells.

Muscle-fiber type in livestock skeletal muscles influences meat quality, but the underlying mechanisms remain unclear. We previously showed that Homeobox A11 (Hoxa11) and Homeobox A13 (Hoxa13) are differentially expressed in fast- and slow-twitch muscles, but their effects on the formation of muscle-fiber types and intramuscular fat deposition have not been investigated. Here, our results revealed that overexpression of Hoxa11 and Hoxa13 delayed cell-cycle progression in C2C12 myoblasts, reduced their proliferation, and promoted their differentiation into slow-twitch muscle fibers. Knockdown experiments produced the opposite results. The conditioned media of differentiated C2C12 cells with Hoxa11/Hoxa13 overexpression or knockdown were harvested. Staining results showed that adipogenesis of preadipocytes was significantly promoted by Hoxa13 knockdown C2C12 cell culture medium. Changes in lipid accumulation were due to a reduction in lipid decomposition and an increase in triglyceride synthesis; genes related to fatty-acid synthesis were decreased. In conclusion, our study showed that Hoxa11 and Hoxa13 promote slow-twitch muscle formation and indirectly regulate preadipocyte adipogenesis, which may facilitate meat-quality improvement in the future.

Targeted overexpression of PPARγ in skeletal muscle by random insertion and CRISPR/Cas9 transgenic pig cloning enhances oxidative fiber formation and intramuscular fat deposition.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a master regulator of adipogenesis and lipogenesis. To understand its roles in fiber formation and fat deposition in skeletal muscle, we successfully generated muscle-specific overexpression of PPARγ in two pig models by random insertion and CRISPR/Cas9 transgenic cloning procedures. The content of intramuscular fat was significantly increased in PPARγ pigs while had no changes on lean meat ratio. PPARγ could promote adipocyte differentiation by activating adipocyte differentiating regulators such as FABP4 and CCAAT/enhancer-binding protein (C/EBP), along with enhanced expression of LPL, FABP4, and PLIN1 to proceed fat deposition. Proteomics analyses demonstrated that oxidative metabolism of fatty acids and respiratory chain were activated in PPARγ pigs, thus, gathered more Ca2+ in PPARγ pigs. Raising of Ca2+ could result in increased phosphorylation of CAMKII and p38 MAPK in PPARγ pigs, which can stimulate MEF2 and PGC1α to affect fiber type and oxidative capacity. These results support that skeletal muscle-specific overexpression of PPARγ can promote oxidative fiber formation and intramuscular fat deposition in pigs.

Neuromuscular Specializations of the Human Hypopharyngeal Muscles.

The hypopharyngeal muscles in humans play a vital role in swallowing, speech, and respiration. Increasing evidence indicates that these muscles are specialized to perform life-sustaining upper aerodigestive functions. This review aims to provide current knowledge regarding the key structural, physiological, and biochemical features of the hypopharyngeal muscles, including innervation, contractile properties, histochemistry, biochemical properties, myosin heavy chain (MyHC) expression and regulation, and age-related alterations. These would clarify the unique neuromuscular specializations of the human hypopharyngeal muscles for a better understanding of the functions and pathological conditions of the pharynx and for the development of novel therapies to treat related upper airway disorders.

Medial gastrocnemius muscles fatigue but do not atrophy in paralyzed cat hindlimb after long-term spinal cord hemisection and unilateral deafferentation.

This study of medial gastrocnemius (MG) muscle and motor units (MUs) after spinal cord hemisection and deafferentation (HSDA) in adult cats, asked 1) whether the absence of muscle atrophy and unaltered contractile speed demonstrated previously in HSDA-paralyzed peroneus longus (PerL) muscles, was apparent in the unloaded HSDA-paralyzed MG muscle, and 2) how ankle unloading impacts MG muscle and MUs after dorsal root sparing (HSDA-SP) with foot placement during standing and locomotion. Chronic isometric contractile forces and speeds were maintained for up to 12 months in all conditions, but fatigability increased exponentially. MU recordings at 8-11½ months corroborated the unchanged muscle force and speed with significantly increased fatigability; normal weights of MG muscle confirmed the lack of disuse atrophy. Fast MUs transitioned from fatigue resistant and intermediate to fatigable accompanied by corresponding fiber type conversion to fast oxidative (FOG) and fast glycolytic (FG) accompanied by increased GAPDH enzyme activity in absolute terms and relative to oxidative citrate synthase enzyme activity. Myosin heavy chain composition, however, was unaffected. MG muscle behaved like the PerL muscle after HSDA with maintained muscle and MU contractile force and speed but with a dramatic increase in fatigability, irrespective of whether all the dorsal roots were transected. We conclude that reduced neuromuscular activity accounts for increased fatigability but is not, in of itself, sufficient to promote atrophy and slow to fast conversion. Position and relative movements of hindlimb muscles are likely contributors to sustained MG muscle and MU contractile force and speed after HSDA and HSDA-SP surgeries.

Developmental neuromuscular synapse elimination: Activity-dependence and potential downstream effector mechanisms.

Synaptic connections initially formed during nervous system development undergo a significant transformation during nervous system maturation. Such maturation is essential for the proper architecture and function of the nervous system. Developmental synaptic transformation includes "synapse elimination," a process in which multiple immature presynaptic inputs converge at and compete for control of a common postsynaptic target. This developmental synaptic remodeling is best understood at mammalian neuromuscular junctions. It is well established that neuromuscular activity provides the impetus for the pruning of redundant motor axon inputs. Despite the dominant influence neuromuscular activity exerts on developmental synapse elimination, however, the downstream mechanisms of neuromuscular activity that affect synapse elimination remain poorly understood. Conversely, although several cellular and molecular effector mechanisms are known to impact synapse elimination, it is unclear whether they are modulated by neuromuscular activity. This review discusses how the motor neurons, synaptic glia and muscle fibers each contributes to the developmental phenomenon, and speculates how neuromuscular activity may modulate these contributions.

Association between ACTN3 and acute mountain sickness.

BACKGROUND: During the process of acclimatization, when our organism needs to adjust several metabolic processes in the attempt of establishing a better oxygenation, it is normal that individuals present some symptoms that can lead to the disease of the mountain. However, not everyone presents such symptoms and individuals native of high altitudes regions present genetic differences compared to natives of low altitudes which can generate a better acute adaptation. One of these differences is the higher proportion of type I muscle fibers, which may originate from the R577X polymorphism of the ACTN3 gene. The aim of this study was to compare the response of individuals with different ACTN3 genotypes at simulated 4500 m altitude on the presence of Acute Mountain Sickness (AMS) symptoms. Twenty-three volunteers (RR = 7, RX = 8, XX = 8) spent 4 hours exposed to a simulated altitude of 4500 m inside a normobaric hypoxia chamber. Lactate and glucose concentrations, SpO2, heart rate and the symptoms of AMS were analyzed immediately before entering the chamber and at each hour of exposure. Statistical analysis was performed using IBM SPSS Statistics 21 software. RESULTS: Our results point to an association between AMS symptoms and the presence of R allele from R577X polymorphism. CONCLUSION: We conclude that individuals with at least one R allele of the R577X polymorphism seems to be more susceptible to the effects of hypoxia during the acclimatization process and may develop AMS symptoms.