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

Borzykh, A. A.; Zhedyaev, R. Y.; Ponomarev, I. I.; Vepkhvadze, T. F.; Zgoda, V. G.; Orlova, M. A.; Vavilov, N. E.; Lednev, E. M.; Sharlo, K. A.; Babkova, A. R.; Makhnovskii, P. A.; Shenkman, B. S.; Rukavishnikov, I. V.; Orlov, O. I.; Tomilovskaya, E. S.; Popov, D. V.

doi:10.1101/2024.09.18.613609

bioRxiv · 10.1101/2024.09.18.613609

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

Borzykh, A. A.·Zhedyaev, R. Y.·Ponomarev, I. I.·Vepkhvadze, T. F.·Zgoda, V. G.·Orlova, M. A.·Vavilov, N. E.·Lednev, E. M.·Sharlo, K. A.·Babkova, A. R.·Makhnovskii, P. A.·Shenkman, B. S.·Rukavishnikov, I. V.·Orlov, O. I.·Tomilovskaya, E. S.·Popov, D. V.

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Abstract

PurposeThis study investigated the effects of a one-week disuse, both with and without low-intensity neuromuscular electrical stimulation - a safe (non-traumatic) approach to prevent the loss of muscle mass, on the functional capacities and gene expression in thigh and calf muscles. MethodsThis study assessed the efficiency of low-intensity ([~]10% of maximal voluntary contraction) electrical stimulation in preventing the negative effects of 7-day disuse (dry immersion without and with daily stimulation) 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. ResultsApplication of electrical stimulation during dry immersion prevented a decrease in the maximal strength and a slight reduction in aerobic performance of the knee extensors, as well as a decrease in maximal (intrinsic) 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 slightly accelerated the decline in the maximal strength and muscle fiber cross-sectional area, which appears to be related to the activation of inflammatory genes. ConclusionThe data obtained open up broad prospects for the use of low-intensity electrical stimulation to prevent the negative effects of disuse for "mixed" muscles, meanwhile, the optimization of the stimulation protocol is required for "slow" muscles. Practitioner PointsO_LILow-intensity electrical myostimulation is often used as an alternative to exercise and high-intensity electrical stimulation to prevent the loss of muscle mass and function in patients with severe chronic diseases and in spaceflight. However, its effect on muscles with different functional capacities remains uncertain. C_LIO_LIOne week of disuse (dry immersion) lead to a comparable decrease in the maximal strength and (intrinsic) mitochondrial respiration in both the ankle plantar flexors/soleus muscle and the knee extensors/vastus lateralis muscle. Meanwhile changes in gene expression (transcriptome) were three times more pronounced in the soleus muscle than in the vastus lateralis muscle. C_LIO_LIApplication of electrical stimulation during disuse prevented most of the negative effects of disuse in the knee extensors/vastus lateralis muscle, but accelerated the decline in the maximal strength/muscle fiber cross-sectional area in the ankle plantar flexors/soleus muscle, which may be related to the activation of genes regulating the inflammatory response. C_LI

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Borzykh, A. A., Zhedyaev, R. Y., Ponomarev, I. I., Vepkhvadze, T. F., Zgoda, V. G., Orlova, M. A., Vavilov, N. E., Lednev, E. M., Sharlo, K. A., Babkova, A. R., Makhnovskii, P. A., Shenkman, B. S., Rukavishnikov, I. V., Orlov, O. I., Tomilovskaya, E. S., Popov, D. V.. 2024-09-19. Multidirectional effect of low-intensity electrical myostimulation on gene expression and phenotype in thigh and calf muscles after one week of disuse. https://doi.org/10.1101/2024.09.18.613609

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