The importance of neurotrophin 3 (NT-3) for motor control prompted us to ask the question whether direct electrical stimulation of low-threshold muscle afferents, strengthening the proprioceptive signaling, could increase the endogenous pool of this neurotrophin and its receptor TrkC in the Hoffmann-reflex circuitry. The effects were compared with those on brain-derived neurotrophic factor (BDNF) and its TrkB receptor. Stimulation of the tibial nerve, activating low-threshold proprioceptive fibers, produced a strong increase of NT-3 protein in in the soleus muscle and in the lumbar L3-6 segments of the spinal cord, where motoneurons innervating majority of hindlimb muscles are located. An effect on BDNF protein level was minor, although both NT-3 and BDNF are synthesized in activity-dependent manner. Changes in NT-3 and BDNF protein level corresponded to the changes in their transcripts in L3-6 segments but not in the soleus muscle. We disclosed tissue-specificity of TrkC mRNA and TrkB mRNA responses suggesting that applied stimulation leads to sensitization of the soleus muscle to NT-3. The possibility of increasing NT-3/TrkC with minor effects on BDNF/TrkB signaling in the neuromuscular system, by means of low-threshold electrical stimulation of peripheral nerves, which in humans might be applied in non-invasive way, offers an attractive therapeutic tool.

PLoS ONE 8(6): e65937. doi:10.1371/journal.pone.0065937.