GLIAL-CELL LINE-DERIVED NEUROTROPHIC FACTOR (GDNF) IS A NEUROTROPHIC FACTOR FOR SENSORY NEURONS - COMPARISON WITH THE EFFECTS OF THE NEUROTROPHINS

We compared the effects of glial cell line-derived neurotrophic factor (GDNF) on dorsal root ganglion (DRG) sensory neurons to that of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and ne urotrophin 3 (NT-3). All of these factors were retrogradely transporte d to subpopulations of sensory neuron cell bodies in the L4/ L5 DRG of neonatal rats. The size distribution of I-125-GDNF-labeled neurons wa s variable and consisted of both small and large DRG neurons (mean of 506.60 mu m(2)). I-125-NGF was preferentially taken up by small neuron s with a mean cross-sectional area of 383.03 mu m(2). Iodinated BDNF a nd NT-3 were transported by medium to large neurons with mean sizes of 501.48 and 529.27 mu m(2), respectively. A neonatal, sciatic nerve ax otomy-induced cell death model was used to determine whether any of th ese factors could influence DRG neuron survival in vivo. GDNF and NGF rescued nearly 100% of the sensory neurons. BDNF and NT-3 did not prom ote any detectable level of neuronal survival despite the fact that th ey underwent retrograde transport. We examined the in vitro survival-p romoting ability of these factors on neonatal DRG neuronal cultures de rived from neonatal rats. GDNF, NGF, and NT-3 were effective in vitro, while BDNF was not. The range of effects seen in the models described here underscores the importance of testing neuronal responsiveness in more than one model. The biological responsiveness of DRG neurons to GDNF in multiple models suggests that this factor may play a role in t he development and maintenance of sensory neurons. (C) 1997 John Wiley & Sons, Inc.