NEUROTROPHIN-3 ADMINISTRATION ATTENUATES DEFICITS OF PYRIDOXINE-INDUCED LARGE-FIBER SENSORY NEUROPATHY

Chronic treatment of adult rats for 2-3 weeks with high doses of pyrid oxine (vitamin B-6) produced a profound proprioceptive loss, similar t o that found in humans overdosed with this vitamin or treated with the chemotherapeutic agent cisplatin. Pyridoxine toxicity was manifest as deficits in simple and precise locomotion and sensory nerve function and as degeneration of large-diameter/large-fiber spinal sensory neuro ns. As assessed quantitatively in a beam-walking task and by EMG recor ding of H waves evoked by peripheral nerve stimulation, coadministrati on of the neurotrophic factor neurotrophin-3 (NT-3; 5-20 mg . kg(-1) . d(-1), s.c.) during chronic pyridoxine treatment largely attenuated t he behavioral and electrophysiological sequelae associated with pyrido xine toxicity. Furthermore, NT-3 administration prevented degeneration of sensory fibers in the dorsal column of the spinal cord, These data are consistent with the evidence that NT-3 is a target-derived neurot rophic factor for muscle sensory afferents and suggest that pharmacolo gical doses of NT-3 may be beneficial in the treatment of large-fiber sensory neuropathies.