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Multidirectional effect of low-intensity electrical myostimulation on gene expression and phenotype in thigh and calf muscles after one week of disuse

ABSTRACT: Low-intensity neuromuscular electrical stimulation (NMES) is often used as an alternative to exercise and high-intensity electrical stimulation to prevent the loss of muscle mass, strength, and endurance in spaceflight and in patients with severe chronic diseases. This study assessed the efficiency of low-intensity (~10% of maximal voluntary contraction) combined (low- and high-frequency) electrical stimulation in preventing the negative effects of weekly disuse (dry immersion without [DI, see a related dataset GSE271607] and with [DI+NMES] daily stimulation; 10 males in each group) on the strength and aerobic performance of the ankle plantar flexors and knee extensors, mitochondrial function in permeabilized muscle fibers, and the proteomic (quantitative mass spectrometry-based analysis) and transcriptomic (RNA-sequencing) profiles of the soleus muscle and vastus lateralis muscle. Application of electrical stimulation during dry immersion prevented a decrease in the maximal strength and a slight reduction in aerobic performance of knee extensors, as well as a decrease in maximal ADP-stimulated mitochondrial respiration and changes in the expression of genes encoding mitochondrial, extracellular matrix, and membrane proteins in the vastus lateralis muscle. In contrast, for the ankle plantar flexors/soleus muscle, electrical stimulation had a positive effect only on maximal mitochondrial respiration, but accelerated the decline in the maximal strength and muscle fiber cross-sectional area, which appears to be associated with the activation of genes regulating the inflammatory response. The data obtained open up broad prospects for the use of low-intensity combined electrical stimulation to prevent the negative effects of disuse for “mixed” muscles, meanwhile, the optimization of the stimulation protocol is required for “slow” muscles.

ORGANISM(S): Homo sapiens

PROVIDER: GSE271606 | GEO | 2024/09/08

REPOSITORIES: GEO

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Project description:Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to simultaneously contract multiple muscle groups. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly via mitochondrial biosynthesis. In this study, we examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for 1 week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague Dawley rats using belt electrodes attached to both ankle joints. In acute stimulation, a significant decrease in glycogen content in the left and right TA and GAS was observed, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES also enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN+electrically stimulated with B-SES (DEN＋ES) groups. After 7 days of treatment, muscle wet weight (n = 8-11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN+ES groups compared to those in the CON group. The DEN+ES group showed significantly higher muscle weight and CSA than the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial and ribosome biogenesis are key events in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 45S (n = 6) levels in the DEN+ES group were higher than those in the DEN group. The mRNA levels of the muscle proteolytic molecules Atrogin-1 and MuRF1 were significantly higher in DEN than in CONT but were suppressed in DEN+ES. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes was effective in preventing denervation-induced atrophy in multiple muscle groups. Unlike twitch contractions, ribosomal biosynthesis plays a key role in tetanic contractions to prevent muscle atrophy.

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Multidirectional effect of low-intensity electrical myostimulation on gene expression and phenotype in thigh and calf muscles after one week of disuse

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