The effect of high-frequency, low-threshold electrical stimulation of peripheral nerves on the pool of neurotrophin 3 in the lumbar spinal cord and soleus muscle of the rat

Locomotor exercise, sufficient to increase expression of brainderived neurotrophic factor and neurotrophin 4 in the lumbar spinal cord, does not affect protein level of neurotrophin 3 (NT-3), as we have shown previously. The effect of 7 days of direct, lowfrequency electrical stimulation of the tibial nerve on expression of NT-3 was also negligible although this stimulation was addressed to low-threshold muscle afferents expressing the NT-3 and its high-affinity receptor trkC. To verify whether upregulation of NT-3 requires stronger stimulation, we maximized efficiency of electrical stimulation. Hoffmann reflex, recorded from the soleus muscle, allowed controlling low-threshold stimulation delivered by cuff electrode implanted over the tibial nerve. Electrodes were implanted bilaterally. The nerve was stimulated unilaterally for 7 days, starting 3 weeks after surgery. The contralateral limb served as a control. Series of 3 rectangular pulses of 200 µs duration and 4 ms inter-pulse intervals were applied every 25 ms in four 20 min sessions daily. NT-3 was evaluated in supernates of homogenates from L1 – L2 and L3 – L6 segments of the spinal cord and in the soleus muscles with ELISA. In intact rats (n=4) NT-3 concentration amounted to 225 pg/mg of protein in the soleus muscle and about 60 pg/mg in lumbar segments of the spinal cord. NT-3 increased by 77% in the soleus muscle on stimulated and by 18% on non-stimulated side, comparing to intact rats. In L3 – L6 segments of the spinal cord the NT-3 was raised by 35% and 15 % on stimulated and non-stimulated side, respectively. In L1 – L2 segments there was bilateral increase of NT-3 by about 30%. We show that high-frequency low-threshold stimulation of the tibial nerve, by means of chronically implanted cuff electrodes, is capable to activate NT-3 protein both in the soleus muscle and in the caudal lumbar spinal cord indicating that also NT-3 expression is regulated in activity-dependent manner. Supported by MSE grant N N401 0480 33.

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