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1Enteric glia mediate neuronal outgrowth through release of neurotrophic factors显示文摘Previous studies have shown that transplanted enteric glia enhance axonal regeneration, reduce tissue damage, and promote functional recovery following spinal cord injury. However, the mechanisms by which enteric glia mediate these beneficial effects are unknown. Neurotrophic factors can promote neuronal differentiation, survival and neurite extension. We hypothesized that enteric glia may exert their protective effects against spinal cord injury partially through the secretion of neurotrophic factors. In the present study, we demonstrated that primary enteric glia cells release nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor over time with their concentrations reaching approximately 250, 100 and 50 pg/mL of culture medium respectively after 48 hours. The biological relevance of this secretion was assessed by incubating dissociated dorsal root ganglion neuronal cultures in enteric glia-conditioned medium with and/or without neutralizing antibodies to each of these proteins and evaluating the differences in neurite growth. We discovered that conditioned medium enhances neurite outgrowth in dorsal root ganglion neurons. Even though there was no detectable amount of neurotrophin-3 secretion using ELISA analysis, the neurite outgrowth effect can be attenuated by the antibody-mediated neutralization of each of the aforementioned neurotrophic factors. Therefore, enteric glia secrete nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and neurotrophin-3 into their surrounding environment in concentrations that can cause a biological effect.Christopher R. Hansebout Kiran Reddy Donald Zhang Michel P. Rathbone 2012Neural Regeneration Research2012,7,28:2
2Inhibition and reversal of growth cone collapse in adult sensory neurons by enteric glia-induced neurotrophic factors显示文摘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.Simon Feng Kiran Reddy Cai-Xin Su Shu-Cui Jiang 2016Neuroimmunology and Neuroinflammation2016,3,1:0
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