Inhibition and reversal of growth cone collapse in adult sensory neurons by enteric glia-induced neurotrophic factors

Aim:Previous studies show enteric glia(EG)-conditioned medium promotes neurite outgrowth in adult dorsal root ganglia(DRG)derived sensory neurons.This EG-conditioned medium contains various neurotrophic factors,including nerve growth factor(NGF),brain-derived neurotrophic factor(BDNF),glial cell line-derived neurotropic factor(GDNF),and neurotrophin-3(NT-3).This study attempts to determine the importance of these neurotrophic factors in enabling DRG-derived sensory neuron axons to overcome the inhibitory guidance cues released from the glial scar.Methods:A Semaphorin 3A(SEMA3A)growth cone collapse model was used on cultured rat DRG.Neutralizing antibodies to each neurotrophic growth factor in question(NGF,BDNF,GDNF and NT-3)were applied to the EG-conditioned medium to evaluate the factor’s individual importance in preventing growth cone collapse.Results:EG-conditioned medium inhibits and reverses growth cone collapse in adult DRG neurons when added either 1 h before or concurrently with SEMA3A.When administered 40 min after the initial SEMA3A-induced collapse,EG-conditioned medium was able to reverse the growth cone collapse.Individual inhibition of all the neurotrophic factors,except for BDNF in the co-treatment setting,resulted in increased growth cone collapse.Conclusion:NGF,BDNF,GDNF,and NT-3 are all variably involved in preventing or reversing SEMA3A-induced growth cone collapse in pre-,co-,and post-treatment time settings.However,no individual neurotrophic factors appear to be essential to promoting neurite outgrowth.