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Povzetek: Previous studies showed that properties of higher‐threshold motor units (MUs) and neuromuscular junction (NMJ) function are preserved during short‐term disuse. This study aimed to test how a longer disuse period affects MU properties, NMJ transmission, and NMJ morphology remodeling. Nine young healthy males (age: 18‐29 years) underwent 21 days of horizontal bed rest. Pre‐ (BR0) and post‐bed rest (BR21), quadriceps maximal voluntary contraction (MVC), and size were assessed. We combined intramuscular electromyography (iEMG) and high‐density surface electromyography (HDsEMG) recordings on the vastus lateralis to assess MU properties at 25% and 50% of MVC. Muscle biopsies and blood samples were also collected. Quadriceps MVC and size decreased at BR21. We found alterations in MU properties at both contraction intensities, including reduced discharge rate, MU potential area changes, and increased complexity. NMJ transmission was found to be reduced at BR21 at 25% MVC. This functional NMJ impairment was biochemically corroborated by an increase in serum C‐terminal agrin fragment concentration, a biomarker of NMJ instability. In addition, a direct assessment of NMJ morphology revealed the presence of some denervated NMJs exclusively at BR21. In conclusion, 21‐day bed rest altered MU properties across different contraction intensities and impaired NMJ transmission with initial signs of remodeling/denervation. Disuse duration appears to be a critical factor, as previous shorter studies failed to detect some of these changes. We believe these findings are clinically relevant for disuse after trauma, surgery, or illness, and may support the development of effective countermeasures.
Ključne besede: disuse, unloading, physical inactivity, electrophysiology, electromyography
Objavljeno v DiRROS: 13.05.2025; Ogledov: 226; Prenosov: 69
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Povzetek: The neuromuscular junction (NMJ) plays a key role in modulating muscle contraction,but the impact of short-term disuse on NMJ structure and function, particularly in older humans,remains unclear. This study aimed to investigate NMJ alterations following 10 days of horizontalbed rest in 10 older males (68.5 ± 2.6 years). Before and after bed rest, vastus lateralis musclebiopsies were obtained to evaluate NMJ morphology, intramuscular EMG (iEMG) was recordedto assess NMJ function and blood samples were collected to determine circulating C-terminal agrinfragment (CAF) concentration, a biomarker of NMJ remodelling. In a sub-cohort of six participantswho had NMJs in both pre- and post-bed rest biopsies, we observed altered NMJ morphology,including reduced overlap between NMJ terminals, as well as increased endplate area and peri-meter. CAF concentration was elevated after bed rest, suggesting ongoing NMJ remodelling. iEMGanalysis showed increased motor unit potential complexity and reduced firing rate. In addition,we observed impaired NMJ transmission, inferred from increased near-fibre jiggle and segmentjitter. These findings suggest that older male individuals are susceptible to NMJ remodelling andimpaired transmission with short-term disuse, providing valuable insights into the morphologicaland functional consequences of inactivity in an ageing population. Our study highlights theimportance of developing interventions for mitigating the detrimental consequences of inactivityon neuromuscular health in older adults, which they frequently experience following injury, trauma,illness or surgery.
Ključne besede: ageing, C-terminal agrin, fragment disuse, electromyography, motor unit, NMJ unloading
Objavljeno v DiRROS: 19.03.2025; Ogledov: 286; Prenosov: 229
Celotno besedilo (2,13 MB)
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Povzetek: Introduction: Sarcopenia is a multifaceted condition affecting between 10 and 16% of the global population, and although multiple classification algorithms exist, no prevalence has been reported for a representative sample of the Slovenian population. Furthermore, multiple behavioural factors, such as malnutrition, physical inactivity, sedentary lifestyle and lower cognitive function, can contribute to the risk of sarcopenia. This study aims to: a) determine sarcopenia prevalence among Slovenian older adults according to different classification algorithms, b) compare the agreement among the algorithms and c) evaluate the relationship between proposed risk factors and sarcopenia. Methods: 654 participants (≥60 years, 30.4% males) have been classified into sarcopenia groups according to eight algorithms, and agreement (Fleiss K) between them was calculated. Additionally, age, sex, nutritional status, physical activity, sedentary levels and cognitive function were assessed as sarcopenia risk/protective factors. Results: The prevalence of sarcopenia according to EWGSOP2 was 4.1%, ranging from 2.1% to 15.3%, when classified by all eight algorithms. Overall agreement between algorithms was weak (K=.429; 95% CI .414 to .444) with 0.6% of participants classified as sarcopenic by all eight algorithms. Adequate nutrition and physical activity were identified as protective factors, while age, lower cognitive function and sedentary lifestyle were considered risk factors. Conclusion: Sarcopenia prevalence among the Slovenian general population was lower than in the global population. We can conclude that different sarcopenia algorithms lead to a different prevalence of sarcopenia. It is of great importance to be cautious when comparing prevalences among studies and to further validate the classification algorithms.
Ključne besede: sarcopenia, prevalence, epidemiology, classification algorithms, risk factors
Objavljeno v DiRROS: 03.03.2025; Ogledov: 247; Prenosov: 120
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Povzetek: Hypokinesia triggers oxidative stress and accelerates the turnover of the glutathione system via the γ-glutamyl cycle. Our study aimed to identify the regulatory checkpoints controlling intracellular glutathione levels. We measured the intermediate substrates of the γ-glutamyl cycle in erythrocytes from 19 healthy young male volunteers before and during a 10-day experimental bed rest. Additionally, we tracked changes in glutathione levels and specific metabolite ratios up to 21 days of bed rest. Using gas chromatography-mass spectrometry and the internal standard technique, we observed a 9 ± 9% decrease in glutathione levels during the first 5 days of bed rest, followed by an 11 ± 9% increase from the 5th to the 10th day, nearly returning to baseline ambulatory levels. The cysteinyl-glycine-to-glutathione ratio, reflecting γ-glutamyl cyclotransferase activity (a key enzyme in glutathione breakdown), rose by 14 ± 22% in the first 5 days and then fell by 10 ± 14% over the subsequent 5 days, again approaching baseline levels. Additionally, the γ-glutamyl cysteine-to-cysteine ratio, indicative of γ-glutamyl cysteine synthetase activity (crucial for glutathione synthesis), increased by 12 ± 30% on day 5 and by 29 ± 41% on day 10 of bed rest. The results observed on day 21 of bed rest confirm those seen on day 10. By calculating the ratio of product concentration to precursor concentration, we assessed the efficiency of these key enzymes in glutathione turnover. These results were corroborated by directly measuring glutathione synthesis and degradation rates in vivo using stable isotope techniques. Our findings reveal significant changes in glutathione kinetics during the initial days of bed rest and identify potential therapeutic targets for maintaining glutathione levels.
Ključne besede: antioxidant, muscle unloading, glutathion turnover, γ-glutamyl cycle, gamma-glutamyl cycle
Objavljeno v DiRROS: 21.11.2024; Ogledov: 388; Prenosov: 1281
Celotno besedilo (1,84 MB)
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Ključne besede: skeletal muscle, conference, reports
Objavljeno v DiRROS: 28.10.2024; Ogledov: 371; Prenosov: 198
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