中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2012, Vol. 7 ›› Issue (28): 2165-2175.

• 原著:周围神经损伤修复保护与再生 •    下一篇

肠胶质细胞通过释放神经营养因子促神经元突起生长

  

  • 收稿日期:2012-04-06 修回日期:2012-07-24 出版日期:2012-10-05 发布日期:2012-10-05

Enteric glia mediate neuronal outgrowth through release of neurotrophic factors

Christopher R. Hansebout 1, 2, Caixin Su 1, 2, Kiran Reddy 1, 2, Donald Zhang 2, 3, Cai Jiang 2, 4, Michel P. Rathbone 2, 4, Shucui Jiang1   

  1. 1 Department of Surgery (Neurosurgery, Neuroscience and Neurobiology), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada 2 Hamilton NeuroRestorative Group (NRG), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada 3 Cleveland Clinic Spine Institute, Cleveland, OH 44195, USA 4 Department of Medicine (Neurology, Neurobiochemistry), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada
  • Received:2012-04-06 Revised:2012-07-24 Online:2012-10-05 Published:2012-10-05
  • Contact: Shucui Jiang, M.D., Ph.D., Associate Professor, Department of Surgery (Neurosurgery, Neuroscience and Neurobiology), Head of Hamilton NeuroRestorative Group (NRG), McMaster University,1280 Main Street West, HSC 4N51, Hamilton, Ontario, Canada L8S 4K1 jiangs@mcmaster.ca
  • About author:Christopher R. Hansebout, Department of Surgery (Neurosurgery, Neuroscience and Neurobiology), Hamilton NeuroRestorative Group (NRG), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada

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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.

Key words: spinal cord injury, dorsal root ganglia, enteric glia, neurotrophic factor, neurite outgrowth, regeneration, cell culture, immunohistochemistry, central nervous system, neuroregeneration