Locomotor Treadmill Training Promotes Soleus Trophism by Mammalian Target of Rapamycin Pathway in Paraplegic Rats

Abstract

Assisted-treadmill training, may be helpful in promoting muscle mass preservation after incomplete spinal cord injury (SCI). However, biological mechanism involved in this process is still not fully understood. This study investigated the effects of locomotor treadmill training on muscle trophism mediated by protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) in paraplegic rats. Adult female Wistar rats underwent an incomplete thoracic SCI induced by compression using an aneurysm clip. After 7 days, injured animals started a 3-week locomotor treadmill training with body weight-support and manual step help. Soleus trophism was measured by muscle weight and transverse myofiber cross-sectional area (CSA). An enzyme-linked immunosorbent assay (ELISA) and western blot analysis were used to detect brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), Akt, mTOR and p70S6K in paretic soleus. Trained animals did not show locomotor improved, but present an increase in muscle weight and myofiber CSA. Furthermore, the levels of Akt, p70S6K phosphorylation, mTOR and TrkB receptor were increased by training in soleus. In contrast, muscle BDNF levels were significantly reduced after training. The results suggest locomotor treadmill training partially reverts/prevents soleus muscle hypotrophy in rats with SCI. Furthermore, this study provided the first evidence that morphological muscle changes were caused by Akt/mTOR/p70S6K signaling pathway and TrkB up-regulation, which may increase the sensitivity of muscle, reducing autocrine signaling pathway demand of BDNF for cell growth.

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Acknowledgements

The authors are grateful to the undergraduate students, Amabile Weber, Jéssyca Vieira, Letícia Rosa and Nicolas Alexsander for their kind assistance in caring for the animals during the survival period.

Funding

This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC, TO 2013TR003379), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil. No competing financial interests exist.

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Authors

Contributions

CCES: study concept and design, acquisition, analysis and interpretation of data and further drafted the manuscript. AM and GRF: acquisition and interpretation of data (notably behavioral analysis), and revision of the manuscript. FB: acquisition and interpretation of data (notably ELISA analysis), and revision of the manuscript. MPC, DDS and ALSR: acquisition and interpretation of data (notably Western blot analysis), and critical revision of the manuscript. ARSS, AS and JI: study concept and design, acquisition and interpretation of data, and critical revision of the manuscript.

Corresponding author

Correspondence to Jocemar Ilha.

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do Espírito Santo, C.C., Secco, D.D., Meireles, A. et al. Locomotor Treadmill Training Promotes Soleus Trophism by Mammalian Target of Rapamycin Pathway in Paraplegic Rats. Neurochem Res 43, 1258–1268 (2018). https://doi.org/10.1007/s11064-018-2543-6

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Keywords

  • Spinal cord injury
  • Treadmill locomotor training
  • Exercise training
  • Muscular atrophy
  • Protein synthesis
  • Neurological rehabilitation