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.

Impact of rehabilitation on volumetric muscle loss in subjects with traumatic spinal cord injury: A systematic review

“…Interestingly, the authors reported that late training groups had preservation of the motoneurons in the spinal cord and larger muscle fibers area in tibialis anterior muscle; in contrast, the SCI-T7 group had higher lesion volume after locomotor training in comparison with the SCI group, demonstrating that identify a locomotor training starting time after the injury is essential to define the best therapeutic window for rehabilitation. Santo et al (2018) investigated the effects of locomotor treadmill training on muscle tropism mediated by protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) in paraplegic adult female Wistar rats underwent an incomplete thoracic SCI induced by compression using an aneurysm clip, and, after 7 days, a 3-week locomotor treadmill training with body weight-support. In particular, trained animals did not show locomotor improvement, but presented an increase in muscle weight and myofiber CSA, confirming the locomotor treadmill training's role in the prevention of soleus muscle hypotrophy in rats with SCI.…”