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Volume 17, Number 1, Issue of January 1, 1997 pp. 470-476
Copyright ©1997 Society for Neuroscience

Adult Mammalian Sensory and Motor Neurons: Roles of Endogenous Neurotrophins and Rescue by Exogenous Neurotrophins after Axotomy

Received July 26, 1996; revised Sept. 27, 1996; accepted Oct. 17, 1996.

John B. Munson³, David L. Shelton², and Stephen B. McMahon¹

¹ Department of Physiology, St Thomas' Hospital Medical School, London SE1 7EH, United Kingdom, ² Department of Neuroscience, Genentech Inc., South San Francisco, California 94080, and ³ Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida 32610

We have tested the ability of neurotrophins to reverse axotomy-induced changes in adult motor and sensory neurons, using the physiological measure of conduction velocity. Five weeks after axotomy, sensory and motor conduction velocities were greatly reduced. NT-3 at 60 µg/d, pumped directly onto the cut nerve stump, largely prevented the change in sensory fibers. Lower doses were less effective, and NT-4/5 was without effect. In contrast, both NT-3 and NT-4/5 were effective at rescuing motoneurons, with similar dose dependencies. This amelioration of physiological deficits in adult mammalian neurons suggests possible therapeutic application of neurotrophins. We have also studied the physiological effects of neurotrophin deprivation on intact peripheral neurons. After 2 weeks of sequestration of trkB ligands (BDNF and NT-4/5), motor, but not sensory, neuron conduction was significantly slowed. Sequestration of NT-3 was found to affect both motor and sensory fiber velocities but more modestly and only with higher doses of sequestering agent. These data therefore suggest that peripherally produced neurotrophins are necessary for the maintenance of normal functional properties of peripheral neurons.

Key words: axotomy; motoneurons; sensory neurons; degeneration; neuropathy; neurotrophin; NT-3; NT-4/5

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