ADULT MAMMALIAN SENSORY AND MOTOR-NEURONS - ROLES OF ENDOGENOUS NEUROTROPHINS AND RESCUE BY EXOGENOUS NEUROTROPHINS AFTER AXOTOMY

We have tested the ability of neurotrophins to reverse axotomy-induced changes in adult motor and sensory neurons, using the physiological m easure of conduction velocity. Five weeks after axotomy, sensory and m otor conduction velocities were greatly reduced. NT-3 at 60 mu g/d, pu mped directly onto the cut nerve stump, largely prevented the change i n sensory fibers. Lower doses were less effective, and NT-4/5 was with out effect. In contrast, both NT-3 and NT-4/5 were effective at rescui ng motoneurons, with similar dose dependencies. This amelioration of p hysiological deficits in adult mammalian neurons suggests possible the rapeutic application of neurotrophins. We have also studied the physio logical effects of neurotrophin deprivation on intact peripheral neuro ns. After 2 weeks of sequestration of trkB ligands (BDNF and NT-4/5), motor, but not sensory, neuron conduction was significantly slowed. Se questration of NT-3 was found to affect both motor and sensory fiber v elocities but more modestly and only with higher doses of sequestering agent. These data therefore suggest that peripherally produced neurot rophins are necessary for the maintenance of normal functional propert ies of peripheral neurons.