Daily brief restraint stress alters signaling pathways and induces atrophy and apoptosis in rat skeletal muscle

Stress. 2010 Mar;13(2):132-41. doi: 10.3109/10253890903089834.


Skeletal muscle protein loss, known as atrophy, occurs during inactivity, disease, and aging. Atrophy may be the result of increased catabolic factors, e.g. glucocorticoids, or reduced influence of anabolic factors, e.g. insulin. The purpose of this study was to investigate atrophy, signaling mechanisms, and apoptosis in a rat model of restraint stress in 40 adult male Wistar rats. Due to the anxiolytic effects of Sutherlandia frutescens, we also determined if any of the molecular events in gastrocnemius muscle would be affected by daily treatment with S. frutescens. Rats were randomly assigned to four experimental groups: control placebo (CP); control Sutherlandia (CS) treatment; Restraint Placebo (RP) and Restraint Sutherlandia (RS) treatment. Restraint resulted in a significant increase in myostatin which was significantly reduced with Sutherlandia treatment. In addition, MyoD expression was significantly attenuated in RP and this effect was also counteracted by Sutherlandia treatment. Restraint also resulted in a significant attenuation of the PI3-Kinase/Akt signaling pathway and increased apoptosis which was reversed with Sutherlandia treatment. This study demonstrates for the first time that psychological stress elevates markers of muscle atrophy and apoptosis, whilst a herbal remedy, Sutherlandia, inhibits apoptosis, and signaling pathways associated with muscle atrophy.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Fabaceae / chemistry
  • Male
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / pathology*
  • Muscular Atrophy / etiology
  • Muscular Atrophy / pathology*
  • MyoD Protein / biosynthesis
  • Myostatin / biosynthesis
  • Phosphatidylinositol 3-Kinases / physiology
  • Plant Extracts / pharmacology
  • Proto-Oncogene Proteins c-akt / physiology
  • Rats
  • Rats, Wistar
  • Restraint, Physical*
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Stress, Psychological / pathology
  • Stress, Psychological / physiopathology*
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Muscle Proteins
  • MyoD Protein
  • Myostatin
  • Plant Extracts
  • Tripartite Motif Proteins
  • Fbxo32 protein, rat
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, rat
  • Ubiquitin-Protein Ligases
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases