Few days of unloading are sufficient to induce a decline of skeletal muscle mass and function; notably, contractile force is lost at a faster rate than muscle mass.r The reasons behind this disproportionate loss of muscle force are still poorly understood. r We provide strong evidence of two mechanisms only hypothesized until now for the rapid muscle force loss in only 10 days of bed rest.r Our results show that an initial neuromuscular junction instability, accompanied by alterations in the innervation status and impairment of single fibre sarcoplasmic reticulum function contribute to the loss of contractile force in front of a preserved myofibrillar function and central activation capacity.r Early onset of neuromuscular junction instability and impairment in calcium dynamics involved in excitation-contraction coupling are proposed as eligible determinants to the greater decline in muscle force than in muscle size during unloading.
The frequency of micronuclei resulting from chromosome breaks, and that of micronuclei deriving from spindle disturbances was determined in exfoliated cells of the human buccal mucosa in 50 normal individuals. Several confounding factors, such as age, smoking habits, alcohol consumption, etc., were taken into account. While the frequencies of micronuclei resulting from chromosome breaks and of cells with this kind of micronuclei were about double in smokers as compared with non-smokers, the difference being highly statistically significant, the frequencies of cells with spindle disturbances were almost the same in the two groups. No statistically significant correlation was found for any of the other variables examined. In two patients suffering from cancer of the oral cavity the variation of the frequency of the micronuclei during the progress of radiotherapy and following its interruption was determined. It was found that gamma rays induced only micronuclei resulting from chromosome breaks, whose frequency increased linearly with the applied dose, and was lowered to the initial background level 7-12 days after the end of radiotherapy.
Electrophysiological alterations of the neuromuscular junction (NMJ) and motor unit potential (MUP) with unloading are poorly studied. We aimed to investigate these aspects and the underlying molecular mechanisms with short‐term unloading and active recovery (AR). Eleven healthy males underwent a 10‐day unilateral lower limb suspension (ULLS) period, followed by 21‐day AR based on resistance exercise. Quadriceps femoris (QF) cross‐sectional area (CSA) and isometric maximum voluntary contraction (MVC) were evaluated. Intramuscular electromyographic recordings were obtained during 10% and 25% MVC isometric contractions from the vastus lateralis (VL). Biomarkers of NMJ molecular instability (serum c‐terminal agrin fragment, CAF), axonal damage (neurofilament light chain) and denervation status were assessed from blood samples and VL biopsies. NMJ and ion channel transcriptomic profiles were investigated by RNA‐sequencing. QF CSA and MVC decreased with ULLS. Increased CAF and altered NMJ transcriptome with unloading suggested the emergence of NMJ molecular instability, which was not associated with impaired NMJ transmission stability. Instead, increased MUP complexity and decreased motor unit firing rates were found after ULLS. Downregulation of ion channel gene expression was found together with increased neurofilament light chain concentration and partial denervation. The AR period restored most of these neuromuscular alterations. In conclusion, the human NMJ is destabilized at the molecular level but shows functional resilience to a 10‐day unloading period at least at relatively low contraction intensities. However, MUP properties are altered by ULLS, possibly due to alterations in ion channel dynamics and initial axonal damage and denervation. These changes are fully reversed by 21 days of AR.
Key points
We used integrative electrophysiological and molecular approaches to comprehensively investigate changes in neuromuscular integrity and function after a 10‐day unilateral lower limb suspension (ULLS), followed by 21 days of active recovery in young healthy men, with a particular focus on neuromuscular junction (NMJ) and motor unit potential (MUP) properties alterations.
After 10‐day ULLS, we found significant NMJ molecular alterations in the absence of NMJ transmission stability impairment. These findings suggest that the human NMJ is functionally resilient against insults and stresses induced by short‐term disuse at least at relatively low contraction intensities, at which low‐threshold, slow‐type motor units are recruited.
Intramuscular electromyography analysis revealed that unloading caused increased MUP complexity and decreased motor unit firing rates, and these alterations could be related to the observed changes in skeletal muscle ion channel pool and initial and partial signs of fibre denervation and axonal damage.
The active recovery period restored these neuromuscular changes.
Ultrasound (US) imaging has been widely used in both research and clinical settings to evaluate the morphological and mechanical properties of muscle and tendon. In elite sports scenarios, a regular assessment of such properties has great potential, namely for testing the response to training, detecting athletes at higher risks of injury, screening athletes for structural abnormalities related to current or future musculoskeletal complaints, and monitoring their return to sport after a musculoskeletal injury. However, several practical and methodological aspects of US techniques should be considered when applying this technology in the elite sports context. Therefore, this narrative review aims to (1) present the principal US measures and field of applications in the context of elite sports; (2) to discuss, from a methodological perspective, the strengths and shortcomings of US imaging for the assessment of muscle and tendon properties; and (3) to provide future directions for research and application.
To evaluate the frequency of micronucleated lymphocytes in a normal population, 45 healthy subjects were analysed by using a modified cytochalasin B block method; the influence of some confounding factors (sex, age, smoking, etc.) were taken into account. Using a stepwise regression test smoking habits were found to have a statistically significant influence on the frequency of micronucleated cells and micronuclei. In addition, the mitotic and proliferative indexes, and the frequency of micronucleated lymphocytes, at different culture times, were studied in four healthy subjects. Based on the results we suggest that cytochalasin B be added to cultures no later than the 42nd hour.
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