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.