Tensile Loading Induces Translational Signaling in Peripheral Nerve

Abstract

Tension is a key determinant of neuronal growth and function. Though nerve stretch (strain) is often associated with damage, moderate strain at a low strain rate encourages axonal outgrowth. To understand the interplay between nerve tension and biological signaling, and as an early step to assess the potential of mechanical loading for peripheral nerve regeneration, we examined the activation of signaling pathways associated with local synthesis of new proteins in stretched nerves. Sciatic nerves of anesthetized rats were exposed bilaterally and strained 0% or 20% for 6 hrs. EMG was used to assess neuromuscular conduction latency, and quantitative immunoblotting was used to assess activation of mTOR/S6 signaling pathways (ratio of phospho to total mTOR/S6), the expression of beta‐actin, neurofilaments (NF), tubulin, and myelin basic protein, and NF phosphorylation (ratio of phospho to total NF). Repeated‐measures ANOVA/Sidak's post‐hoc was used to test the effect of strain on EMG parameters and protein expression. Stretch for 6 hours did not alter compound muscle action potential latency (p>0.9). mTOR and S6 activation were significantly increased in stretched nerves by 40% each (p<0.02), indicating a strong local translational response. Significant increases in expression of beta‐actin (125%; p<0.01) and myelin basic protein (60%; p<0.01) and in NF phosphorylation (55%; p<0.03) with stretch suggest structural remodeling in neuronal and myelinating cells to accommodate the demand for increased volume and structural integrity in lengthened nerves. Nerve stretch did not impair function and may provide a novel approach to peripheral nerve repair.