Search Results (65)

Background/Objectives: The neuromuscular junction (NMJ) is the area where peripheral nerves communicate with muscle tissue. Muscle injury can occur as part of an acute degenerative process at the NMJ. This study aims to investigate the remodeling of the NMJ after a muscle injury in an experimental model. Methods: We used sixty male Wistar rats divided into five groups: a control group (C) and four muscle injury groups (MI) at different time points: 0 h, 24 h, 48 h, and 7 d after injury. We subjected the right hind limb to muscle injury and dissected the gastrocnemius muscles for analysis. We employed light microscopy to examine cell nuclei and the connective tissue, immunostaining to identify and measure the pre- and postsynaptic regions as well as calcium channels (P/Q), and real-time PCR to assess the gene expression of NRG1 and Agrin. Results: Our findings revealed an accumulation of nuclei and connective tissue in the acute injury groups (0 to 48 h). The morpho-quantitative analyses showed that the presynaptic structures and calcium channels underwent similar remodeling due to their morpho-functional relationship. Meanwhile, the postsynaptic receptors were significantly affected by the degenerative and inflammatory processes. These results can be linked to increased expression of NRG1 and Agrin in the acute injury groups. Conclusions: In conclusion, the synaptic regions displayed substantial adaptations within the first 48 h, with the presynaptic region recovering rapidly and the postsynaptic region recovering slowly. This relationship suggests that significant increases in Agrin and NRG1 play a crucial role in maintaining the integrity of these structures. Full article

Background/objectives: Multiple systemic treatments are available for metastatic castration-resistant prostate cancer (mCRPC), with unclear safety profiles. This study seeks to describe the safety determined in randomized clinical trials of a systemic treatment for mCRPC and whether safety differs by age. Methods: We utilized individual patient data from industry-funded phase 2/3 trials in mCRPC on abiraterone acetate (AA). Vivli, a clinical trial repository site, was used. One investigator independently performed screening. Relative effects of treatment were assessed with frequencies and odds of serious adverse events (SAEs). The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. Subgroup analysis measured odds of SAEs as modified by age. Results: We identified 14 trials with 4296 patients. The median age of participants was 69 years. Nearly all participants experienced at least one adverse event (98.4% abiraterone, 97.3% standard of care [SOC]). More serious adverse events (grade 3 or 4) and deaths (grade 5) occurred in those receiving SOC (71.8%) compared to abiraterone (64.1%). The most frequent adverse event category was “Musculoskeletal and Connective Tissue Disorders”. The most frequent event types included anemia, back pain, hypertension, fatigue, hypokalemia, and bone pain. The odds of all events were lower in those receiving abiraterone compared to SOC. Odds of a serious musculoskeletal event were lower in older subjects by 22% (OR 0.78; 95% CI 0.63, 0.96). Conclusions: In this IPD meta-analysis, abiraterone acetate provides no greater risk of SAE in those receiving abiraterone than those receiving SOCs. Patients in the RCTs are younger and healthier than those in the general population; consequently, the results of RCTS might not be applied to the general population, especially those under-represented in the RCTs. There is a need to further evaluate abiraterone-related fractures and neuromuscular toxicities (NMTs) as key outcomes to gain insight into risk factors related to these adverse events. A real-world prospective study is warranted to examine the overall risks and benefits associated with treatment. Full article

Muscle wasting and weakness are critical clinical problems that limit mobility and independence, reduce health span, and increase the risk of physical disability. The molecular basis for this has not been fully determined. Klotho expression is downregulated in conditions associated with muscle wasting, including aging, chronic kidney disease, and myopathy. The objective of this study was to investigate a mechanistic role for Klotho in regulating muscle wasting and weakness. Body weight, lean mass, muscle mass, and myofiber caliber were reduced in Klotho-deficient mice. In the tibialis anterior muscle of Klotho-null mice, type IIa myofibers were resistant to changes in size, and muscle composition differed with a higher concentration of type IIb fibers to the detriment of type IIx fibers. Glycolytic GPDH enzymatic activity also increased. Klotho-deficient mice showed impaired muscle contractility, with reduced twitch force, torque, and contraction–relaxation rates. RNA sequencing revealed upregulation of synaptic and fetal sarcomeric genes, prompting us to examine muscle innervation. Klotho deficiency led to neuromuscular junction remodeling, myofiber denervation, and functional motor unit loss. Loss of motor units correlated with absolute torque. Collectively, these findings reveal a novel mechanism through which systemic Klotho deficiency disrupts muscle synapses and motor unit connectivity, potentially contributing to muscle wasting and weakness. Full article

Osteosarcopenia is a widespread geriatric condition resulting from the coexistence of osteoporosis and sarcopenia, where the connection between bone and muscle is, in part, driven by bone–muscle crosstalk. Given the close, reciprocal influence of muscle on nerve, and vice versa, it is not surprising that there are corresponding aging changes in the biochemistry and morphology of the neuromuscular junction (NMJ). Indeed, degeneration of motor neurons and progressive disruption of the neuromuscular connectivity were observed in old age. Extracellular vesicles (EVs) derived from human amniotic fluid stem cells (hAFSC), exhibiting antioxidant properties, which can also explain their anti-aging and cytoprotective effects, can be considered as potential treatment for age-related diseases. To study cell interactions under both healthy and pathological conditions occurring in musculo–skeletal apparatus, we developed a three-culture system exploiting the use of well-known transwell supports. This system allows both myotubes and neurons, eventually treated with EVs, and osteoblasts, induced to osteoporosis, to interact physically and biochemically. Collectively, this method allowed us to understand how the modifications induced in osteoblasts during bone disorders trigger a cascade of detrimental effects in the muscle and neuron parts. Moreover, we demonstrated the efficacy of hAFSC-EVs in preventing NMJ dysfunction, muscle atrophy, and osteoblast impairment. Full article

Spinal Muscular Atrophy (SMA) is a genetic disorder characterized by the progressive loss of motor neurons and consequent muscle atrophy. Although SMN-targeted therapies have significantly improved survival and motor outcomes, residual muscle weakness remains a major clinical challenge, particularly in patients treated later in the disease course. Myostatin, a potent negative regulator of skeletal muscle mass, has emerged as a promising therapeutic target to address this gap. This review summarizes the preclinical and clinical evidence supporting the modulation of the myostatin pathway in SMA. Preclinical studies have demonstrated that inhibiting myostatin, especially when combined with SMN-enhancing agents, can increase muscle mass, improve motor function, and enhance neuromuscular connectivity in SMA mouse models. These findings provide a strong rationale for translating myostatin inhibition into clinical practice as an adjunctive strategy. Early clinical trials investigating myostatin inhibitors have shown favorable safety profiles and preliminary signs of target engagement. However, large-scale trials have yet to demonstrate widespread, robust efficacy across diverse patient populations. Despite this, myostatin pathway inhibition remains a compelling approach, particularly when integrated into broader treatment paradigms aimed at enhancing motor unit stability and function in individuals with SMA. Further clinical research is essential to validate efficacy, determine optimal timing, and define the patient subgroups most likely to benefit from myostatin-targeted therapies. Full article

Background/Objectives: Soccer players, particularly females, exhibit an increased risk of both concussions and Anterior Cruciate Ligament (ACL) injuries. Emerging evidence suggests that neurcognitive deficits following concussions may impair neuromuscular control, increasing ACL injury susceptibility. This study aims to explore the interplay between concussions, neuromuscular deficits, and ACL injury risk, while proposing targeted prevention strategies. Methods: A comprehensive review of current literature was conducted to analyze the biomechanical and neurophysiological impact of concussions on ACL injury risk. Key areas investigated include the effect of sub-concussive impacts on proprioception, reaction time, and postural stability, as well as sex-based differences in injury susceptibility. Results: Findings indicate that post-concussion neuromuscular impairments—such as altered proprioception, delayed reaction times, and compromised joint stability—heighten ACL injury risk. Female athletes, due to biomechanical and hormonal factors, are particularly vulnerable. Preventive measures, including neuromuscular training, cervical spine strengthening, and optimized return-to-play protocols, are essential to mitigate these risks. Conclusions: Longitudinal research is needed to further elucidate the connection between head trauma and ACL injuries. Implementing evidence-based interventions and policy changes, such as modifying heading exposure in youth athletes, may enhance player safety and reduce long-term injury burden in female soccer players. Full article

This study systematically reviews the role of the cortex in gait control by analyzing connectivity between electroencephalography (EEG) and electromyography (EMG) signals, i.e., neuromuscular connectivity (NMC) during walking. We aim to answer the following questions: (i) Is there significant NMC during gait in a healthy population? (ii) Is NMC modulated by gait task specifications (e.g., speed, surface, and additional task demands)? (iii) Is NMC altered in the elderly or a population affected by a neuromuscular or neurologic disorder? Following PRISMA guidelines, a systematic search of seven scientific databases was conducted up to September 2023. Out of 1308 identified papers, 27 studies met the eligibility criteria. Despite large variability in methodology, significant NMC was detected in most of the studies. NMC was able to discriminate between a healthy population and a population affected by a neuromuscular or neurologic disorder. Tasks requiring higher sensorimotor control resulted in an elevated level of NMC. While NMC holds promise as a metric for advancing our comprehension of brain–muscle interactions during gait, aligning methodologies across studies is imperative. Analysis of NMC provides valuable insights for the understanding of neural control of movement and development of gait retraining programs and contributes to advancements in neurotechnology. Full article

Background: Amyotrophic lateral sclerosis (ALS) is a rare, progressive, and incurable disease characterized by muscle weakness and paralysis. Recent studies have explored a possible link between ALS pathophysiology and mTOR signaling. Recent reports have linked the accumulation of protein aggregates, dysfunctional mitochondria, and homeostasis to the development of ALS. mTOR plays a pivotal role in controlling autophagy and affecting energy metabolism, in addition to supporting neuronal growth, plasticity, and the balance between apoptosis and autophagy, all of which are important for homeostasis. Aim: This mini-review approaches the regulatory roles of mTOR signaling pathways, their interaction with other metabolic pathways, and their potential to modulate ALS progression. Significance: It discusses how these metabolic signaling pathways affect the neuromuscular junction, producing symptoms of muscle weakness and atrophy similar to those seen in patients with ALS. The discussion includes the concepts of neurocentric and peripheral and the possible connection between mTOR and neuromuscular dysfunction in ALS. Conclusions: It highlights the therapeutic potential of mTOR signaling and interconnections with other metabolic routes, making it a promising biomarker and therapeutic target for ALS. Full article

The gut–brain axis (GBA) represents a sophisticated bidirectional communication system connecting the central nervous system (CNS) and the gastrointestinal (GI) tract. This interplay occurs primarily through neuronal, immune, and metabolic pathways. Dysbiosis in gut microbiota has been associated with multiple neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). In recent years, fecal microbiota transplantation (FMT) has gained attention as an innovative therapeutic approach, aiming to restore microbial balance in the gut while influencing neuroinflammatory and neurodegenerative pathways. This review explores the mechanisms by which FMT impacts the gut–brain axis. Key areas of focus include its ability to reduce neuroinflammation, strengthen gut barrier integrity, regulate neurotransmitter production, and reinstate microbial diversity. Both preclinical and clinical studies indicate that FMT can alleviate motor and cognitive deficits in PD and AD, lower neuroinflammatory markers in MS, and enhance respiratory and neuromuscular functions in ALS. Despite these findings, several challenges remain, including donor selection complexities, uncertainties about long-term safety, and inconsistencies in clinical outcomes. Innovations such as synthetic microbial communities, engineered probiotics, and AI-driven analysis of the microbiome hold the potential to improve the precision and effectiveness of FMT in managing neurodegenerative conditions. Although FMT presents considerable promise as a therapeutic development, its widespread application for neurodegenerative diseases requires thorough validation through well-designed, large-scale clinical trials. It is essential to establish standardized protocols, refine donor selection processes, and deepen our understanding of the molecular mechanisms behind its efficacy. Full article

Endurance performance is primarily determined by three key physiological pillars: maximal oxygen uptake (VO₂max), anaerobic threshold, and economy of movement. Recent research has suggested physiological resilience as a potential fourth dimension, referring to an athlete’s ability to sustain performance despite accumulating fatigue. While the role of genetic factors in endurance has been widely studied, their influence on these pillars, particularly on fatigue resistance and long-term adaptation, remains an area of growing interest. This narrative review explores the genomic basis of endurance performance, analyzing genetic contributions to oxygen transport, metabolic efficiency, muscle composition, and recovery. Additionally, it discusses how genetic variability may modulate an athlete’s response to training, including aspects of physiological adaptation, injury susceptibility, sleep, and nutrition. The review highlights physiological resilience in the context of endurance sports, discussing its connection to neuromuscular and metabolic regulation. By integrating genetic insights with established physiological principles, this review provides a comprehensive perspective on endurance adaptation. Future research directions are outlined to enhance our understanding of the genetic underpinnings of endurance, with implications for personalized training and performance optimization. Full article

Background: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder characterized by the degeneration of alpha motor neurons in the spinal cord, leading to progressive proximal muscle weakness and paralysis. SMA is clinically categorized into four phenotypes based on age of onset and motor function achieved. Patients with SMA type 3 (juvenile, Kugelberg-Welander disease) initially have the ability to walk unaided, but experience a gradual decline in motor abilities over time. However, their lifespan is not affected by the presence of the disease. Leptin, a cytokine-like hormone secreted by adipocytes, has receptors widely distributed in musculoskeletal tissues. Several studies suggest that adiponectin deficiency contributes to the development of insulin resistance, with lower adiponectin levels closely associated with greater insulin resistance and hyperinsulinemia. However, the role of adiponectin in different types of sarcopenia and its connection to insulin sensitivity remains controversial. The purpose of this study was to measure leptin and adiponectin levels in patients with SMA type 3 and explore their association with markers of insulin sensitivity. Methods: This cross-sectional study included 23 adult patients with SMA type 3 (SMA group) and 18 community-based healthy volunteers (control group), conducted from July 2020 to September 2024. Anthropometric parameters, body composition, body fat percentage, surrogate markers of insulin sensitivity (Homeostasis model assessment of insulin resistance index—HOMA-IR and ISI Matsuda), and circulating levels of leptin and adiponectin were measured in all participants. Results: Insulin resistance was present in 91.3% of patients with SMA type 3, as determined by HOMA-IR and ISI Matsuda insulin sensitivity markers. In the control group, 64.7% had insulin resistance (IR) according to HOMA-IR, while 44.4% met the ISI Matsuda criterion for IR, showing a significant difference in peripheral insulin sensitivity between groups. A significant difference in serum adiponectin levels was observed between patients with SMA type 3 and the control group, whereas there was no significant difference in serum leptin concentrations. High adiponectin levels were observed in 50% of patients with SMA type 3. In the healthy control group, adiponectin levels positively correlated with ISI Matsuda and negatively correlated with HOMA-IR, confirming the insulin-sensitizing role of adiponectin. However, this correlation was not observed in patients with SMA type 3. Conclusions: Our results suggest that in this specific type of hereditary neuromuscular disease, the interplay between sarcopenia and insulin leads to adiponectin resistance, challenging the canonical narrative between insulin sensitivity and adiponectin, and indicating a need for further research. Full article

Multiple-hop tests are commonly used in both performance and rehabilitation settings to assess neuromuscular function. This study aimed to explore the relationship between hop performance and sprint ability. Specifically, it focused on three goals: (1) examining the connection between 3-Hop and 5-Hop distances and sprint performance and comparing the strength of relationship between hop kinetics and sprint times; (2) investigating two methods of calculating the 3-Hop and 5-Hop Reactive Strength Indexes (RSI_hors) and their relationship to sprinting; and (3) assessing whether hop ratios or kinetic variables could distinguish sprinters of varying abilities. Forty-four male sportsmen participated, completing 3-Hop and 5-Hop tests and sprint times (5–45 m) over 54 inground force platforms. Ground reaction forces (GRFs) were collected during hop trials and horizontal and vertical hop propulsive and braking kinetics were determined. Results showed strong negative correlations between hop distances and sprint times (r = −0.700 to −0.796), while kinetic variables showed weaker relationships with sprint performance (r = −0.554 to 0.017). RSI_hor, derived from hop distance, correlated more strongly with sprint performance than RSI_hor from flight time. Hop ratios (5-Hop/3-Hop) did not differentiate fast from slow sprinters, and maximal vertical force and horizontal propulsive impulse were the best predictors of 10 m and 40 m sprint times. These findings suggest that hop distance and RSI_hor are valuable tools for assessing sprint performance and reactive strength. Full article

In general, the nerve cells of the peripheral nervous system regenerate normally within a certain period after the physical damage of their axon. However, when peripheral nerves are transected by trauma or tissue extraction for cancer treatment, spontaneous nerve regeneration cannot occur. Therefore, it is necessary to perform microsurgery to connect the transected nerve directly or insert a nerve conduit to connect it. In this study, we applied human tonsillar mesenchymal stem cell (TMSC)-derived Schwann cell-like cells (TMSC-SCs) to facilitate nerve regeneration and prevent muscle atrophy after neurorrhaphy. The TMSC-SCs were manufactured in a good manufacturing practice facility and termed neuronal regeneration-promoting cells (NRPCs). A rat model of peripheral nerve injury (PNI) was generated and a mixture of NRPCs and fibrin glue was transplanted into the injured nerve after neurorrhaphy. The application of NRPCs and fibrin glue led to the efficient induction of sciatic nerve regeneration, with the sparing of gastrocnemius muscles and neuromuscular junctions. This sparing effect of NRPCs toward neuromuscular junctions might prevent muscle atrophy after neurorrhaphy. These results suggest that a mixture of NRPCs and fibrin glue may be a therapeutic candidate to enable peripheral nerve and muscle regeneration in the context of neurorrhaphy in patients with PNI. Full article

Background: Choline is an essential nutrient required for proper cell functioning. Due to its status as a precursor to acetylcholine, an important neurotransmitter connected to cognition and neuromuscular function, maintaining or enhancing choline levels is of interest. Supplementation with alpha-glycerylphosphorycholine (A-GPC) can maintain choline levels, but its ability to offer support towards cognition remains an area of ongoing research. Methods: Using a randomized, double-blind, placebo-controlled, crossover approach, 20 resistance-trained males (31.3 ± 11.0 years, 178.6 ± 7.3 cm, 84.6 ± 11.4 kg, 15.4 ± 5.6% body fat) consumed either a placebo (PL), 630 mg A-GPC (HD), or 315 mg (LD) A-GPC (GeniusPure^®, NNB Nutrition, Nanjing, China). After resting hemodynamic assessments, participants took their assigned dose and had cognitive assessments (Stroop, N-Back, and Flanker), visual analog scales, and hemodynamics evaluated 60 min after ingestion. All participants then warmed up and completed vertical jumps and bench press throws before completing a bout of lower-body resistance exercise (6 × 10 repetitions using the Smith squat at a load of 70% 1RM). Venous blood was collected 5, 15, 30, and 60 min after completion of the squat protocol to evaluate changes in growth hormones, and follow-up visual analog scales and cognitive measurements were evaluated 30 min after completing the exercise bout. Results: When compared to PL, changes in Stroop total score were statistically greater after HD (13.0 ± 8.2 vs. 5.2 ± 9.0, p = 0.013, d = 0.61) and LD (10.8 ± 7.7 vs. 5.2 ± 9.0, p = 0.046, d = 0.48) administration, in addition to significantly faster times to complete the Stroop test in the HD group when compared to PL (−0.12 ± 0.09 s vs. −0.05 ± 0.09 s, p = 0.021, d = 0.56). No significant differences between groups were found for the Flanker and N-Back assessments, while a tendency was observed for HD to have faster reaction times when compared to PL during the Flanker test. No group differences were realized for visual analog scales, physical performance, or growth hormone. Statistically significant changes in heart rate and blood pressure were observed in all groups, with all recorded values aligning with clinically accepted normative values. Conclusions: HD and LD A-GPC supplementation significantly increased cognitive performance in a group of young, healthy males as measured by changes in the Stroop Total Score and completion time of the Stroop test. These results offer unique insight into the potential for A-GPC to acutely increase cognition in a group of young, healthy males. While previous research has indicated potential for A-GPC to acutely improve cognition in clinical populations, extending these outcomes to healthy individuals can be potentially meaningful for a wide variety of populations such as athletes, race car drivers, military operators, and other non-athletic populations who desire and have a need to improve their mental performance. This study was retrospectively registered as NCT06690619 on clinicaltrials.gov. Full article

Background: Long-distance swimmers exert energetic, physiological, and neuromuscular demands that must be matched with adequate body composition to improve their performance in long-distance swimming. Objectives: This review aims to compile all available information on energetic and physiological demands, optimal body composition, nutrition, and ergogenic supplements in long-distance swimming. This will provide an understanding of the specific challenges and needs of this sport and will help swimmers and coaches design more effective training and nutrition plans to optimise performance and achieve their goals. Methods: Databases such as Web of Science, SciELO Citation Index, MEDLINE (PubMed), Current Contents Connect, KCI-Korean Journal Database, and Scopus were searched for publications in English using keywords such as swimming, endurance, energy demands, physiological demands, nutrition, body composition, and ergogenic aids, individually or in combination. Results: There is convincing evidence that several physical indicators, such as propulsive surface area, technical, such as stroke rate, and functional, such as hydration strategies, are related to swimming performance and body composition. Each athlete may have a specific optimal body fat level that is associated with improved sporting performance. The nutritional needs of open water swimmers during competition are quite different from those of pool swimmers. Conclusions: Swimmers with an adequate physique have a high body muscle mass and moderately related anaerobic strength both on land and in the water. These general and specific strength capacities, which are given by certain anthropometric and physiological characteristics, are seen throughout the work, as well as ergogenic and nutritional strategies, which have an important impact on long-distance swimming performance. Full article