<p>Skeletal muscles undergo significant atrophy and loss of strength under conditions of disuse/mechanical unloading. Since low-dose lithium treatment has been shown to benefit the musculoskeletal system of mammals, this study sought to investigate the effects of subtherapeutic doses of lithium chloride (LiCl) on the functional properties and markers of protein metabolism in the postural soleus muscle of rats under 7 days of mechanical unloading. Rat hindlimbs were unloaded using the hindlimb suspension (HS) method. Male Wistar rats were divided into four groups: (1) vivarium control (C), (2) vivarium control + LiCl (C + Li), (3) 7-day HS (HS), and (4) 7-day HS + LiCl (HS + Li). LiCl (40&#xa0;mg/kg) was administered intraperitoneally daily throughout the experiment. Structural changes in the muscle were studied using immunohistochemistry. Markers of anabolic and catabolic processes were assessed using Western blotting and PCR. LiCl treatment during HS prevented a decrease in muscle fiber size and slow-to-fast fiber transformation. Additionally, LiCl administration during HS increased the specific maximum force and passive tension of the soleus compared to the control. LiCl administration during HS prevented decreases in GSK-3β (Ser9) and 4E-BP1 (Thr37/46) phosphorylation. Furthermore, LiCl prevented the HS-induced increase in ubiquitin, atrogin-1, MuRF-1, ULK1, and calpain-1 mRNA expression. Thus, daily low-dose LiCl administration during 7-day HS maintained the morphological parameters and increased the functional properties of the rat soleus muscle. This was accompanied by the prevention of the activation of the key proteolytic markers in the soleus muscle.</p>

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Protective effects of low-dose lithium treatment on rat postural muscle under conditions of disuse

  • Timur M. Mirzoev,
  • Sergey A. Tyganov,
  • Olga V. Turtikova,
  • Vitaly E. Kalashnikov,
  • Kristina A. Sharlo,
  • Boris S. Shenkman

摘要

Skeletal muscles undergo significant atrophy and loss of strength under conditions of disuse/mechanical unloading. Since low-dose lithium treatment has been shown to benefit the musculoskeletal system of mammals, this study sought to investigate the effects of subtherapeutic doses of lithium chloride (LiCl) on the functional properties and markers of protein metabolism in the postural soleus muscle of rats under 7 days of mechanical unloading. Rat hindlimbs were unloaded using the hindlimb suspension (HS) method. Male Wistar rats were divided into four groups: (1) vivarium control (C), (2) vivarium control + LiCl (C + Li), (3) 7-day HS (HS), and (4) 7-day HS + LiCl (HS + Li). LiCl (40 mg/kg) was administered intraperitoneally daily throughout the experiment. Structural changes in the muscle were studied using immunohistochemistry. Markers of anabolic and catabolic processes were assessed using Western blotting and PCR. LiCl treatment during HS prevented a decrease in muscle fiber size and slow-to-fast fiber transformation. Additionally, LiCl administration during HS increased the specific maximum force and passive tension of the soleus compared to the control. LiCl administration during HS prevented decreases in GSK-3β (Ser9) and 4E-BP1 (Thr37/46) phosphorylation. Furthermore, LiCl prevented the HS-induced increase in ubiquitin, atrogin-1, MuRF-1, ULK1, and calpain-1 mRNA expression. Thus, daily low-dose LiCl administration during 7-day HS maintained the morphological parameters and increased the functional properties of the rat soleus muscle. This was accompanied by the prevention of the activation of the key proteolytic markers in the soleus muscle.