The Effect of Spontaneous Neuromuscular Activity on the Development of Atrophy of the Functionally Unloaded  m. soleus

K. V. Sergeeva; Сергеева К. В.; K. A. Sharlo; Шарло К. А.; V. E. Kalashnikov; Калашников В. Е.; O. V. Turtikova; Туртикова О. В.; S. A. Tyganov; Тыганов С. А.; B. S. Shenkman; Шенкман Б. С.

doi:10.31857/S0869813923100102

The Effect of Spontaneous Neuromuscular Activity on the Development of Atrophy of the Functionally Unloaded m. soleus

Authors: Sergeeva K.V.¹, Sharlo K.A.¹, Kalashnikov V.E.¹, Turtikova O.V.¹, Tyganov S.A.¹, Shenkman B.S.¹
Affiliations:
1. Institute of Biomedical Problems, Russian Academy of Sciences
Issue: Vol 109, No 10 (2023)
Pages: 1430-1442
Section: EXPERIMENTAL ARTICLES
URL: https://cardiosomatics.ru/0869-8139/article/view/651516
DOI: https://doi.org/10.31857/S0869813923100102
EDN: https://elibrary.ru/XRLLUW
ID: 651516

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Abstract
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Abstract

It is well known that the inactivity of mammalian skeletal muscles leads to the cessation of their electrical activity and is accompanied by atrophic changes in muscle fibers. However, it has been repeatedly noted that starting from the 3rd day of functional unloading, spontaneous rhythmic neuromuscular activity appears, which is the result of a decrease in the expression of the potassium chloride co-transporter KCC-2 in neurons of the lumbar spinal cord. A decrease in the expression of KCC-2 and the onset of autonomous electrical activity of the unloaded muscle can be prevented by the administration of the neuroleptic prochlorperazine. Thus, the aim of this study was to evaluate the structural and signaling effects of the reduced spontaneous activity of the unloaded m.soleus. It was found that daily administration of prochlorperazine to rats under conditions of 7-day simulated gravitational unloading prevented a decrease in the content of the main markers of ribosome biogenesis (c-Myc, 18S rRNA and 28S rRNA), and also partially prevented a decrease in the cross-sectional area of fast and slow muscle fibers in the m.soleus. Morphofunctional changes caused by a decrease of spontaneous activity of the unloaded muscle were accompanied by complete or partial prevention of activation of key proteolytic markers expression (MuRF-1, MAFbx/atrogin-1, ubiquitin). Thus, we assume that spontaneous neuromuscular activity may be a factor that augments muscle atrophy during the first week of functional unloading.

Keywords

skeletal muscle, gravitational unloading, prochlorperazine, spontaneous activity, protein breakdown, ubiquitinligase

References

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