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.