IN-VIVO NEUROTROPHIC EFFECTS OF GDNF ON NEONATAL AND ADULT FACIAL MOTOR-NEURONS

MOTOR neurons require neurotrophic factor(s) for their survival during development and for maintenance of function in adulthood(1-3). In viv o studies have shown that motor neurons respond to a variety of molecu les, including ciliary neurotrophic factor, members of the neurotrophi n family, and the insulin growth factor IGF-1 (refs 3-13). Here we inv estigate the potential motor neuron neurotrophic effects of glial-cell -line-derived neurotrophic factor (GDNF), initially identified as a ne urotrophic factor for substantia nigra dopaminergic neurons(14). We fi nd that GDNF is retrogradely transported, in a receptor-mediated fashi on, by spinal cord motor neurons in neonatal rats. Local application o f GDNF to the transected nerve prevents the massive motor neuron cell death and atrophy that normally follows axotomy in the neonatal period . In adult rats, GDNF administered locally or systemically can markedl y attenuate the lesion-induced decrease of choline acetyltransferase i mmunoreactivity in the facial nucleus. Our data indicate that GDNF has very profound neurotrophic effects in vivo on developing as well as o n adult motor neurons, and is the most potent motor neuron trophic fac tor found so far.