title: Enteric glia mediate neuronal outgrowth through release of neurotrophic factors.
abstract: 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.
authors.affiliation: Department of Surgery (Neurosurgery, Neuroscience and Neurobiology), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada ; Hamilton NeuroRestorative Group (NRG), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Hansebout
authors.affiliation: Department of Surgery (Neurosurgery, Neuroscience and Neurobiology), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada ; Hamilton NeuroRestorative Group (NRG), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada.
authors.forename: Caixin
authors.initials: C
authors.lastname: Su
authors.affiliation: Department of Surgery (Neurosurgery, Neuroscience and Neurobiology), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada ; Hamilton NeuroRestorative Group (NRG), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada.
authors.forename: Kiran
authors.initials: K
authors.lastname: Reddy
authors.affiliation: Hamilton NeuroRestorative Group (NRG), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada ; Cleveland Clinic Spine Institute, Cleveland, OH 44195, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Hamilton NeuroRestorative Group (NRG), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada ; Department of Medicine (Neurology, Neurobiochemistry), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada.
authors.forename: Cai
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Hamilton NeuroRestorative Group (NRG), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada ; Department of Medicine (Neurology, Neurobiochemistry), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada.
authors.forename: Michel P
authors.initials: MP
authors.lastname: Rathbone
authors.affiliation: Department of Surgery (Neurosurgery, Neuroscience and Neurobiology), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada ; Hamilton NeuroRestorative Group (NRG), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada.
authors.forename: Shucui
authors.initials: S
authors.lastname: Jiang
keywords: cell culture; central nervous system; dorsal root ganglia; enteric glia; immunohistochemistry; neurite outgrowth; neuroregeneration; neurotrophic factor; regeneration; spinal cord injury