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Feng et al. Neuroimmunol Neuroinflammation 2016;3:180-8 Neuroimmunology and
DOI: 10.20517/2347-8659.2016.03
Neuroinflammation
www.nnjournal.net
Original Article Open Access
Inhibition and reversal of growth cone
collapse in adult sensory neurons by
enteric glia-induced neurotrophic factors
Simon Feng , Kiran Reddy , Cai-Xin Su , Shu-Cui Jiang 1,2
1,2
1,2
1,2
1 Department of Surgery (Neurobiology), McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada.
2 Hamilton NeuroRestorative Group, McMaster University, Health Sciences Centre, Hamilton, ON L8S 4K1, Canada.
Correspondence to: Prof. Shu-Cui Jiang, Department of Surgery (Neurosurgery, Neuroscience and Neurobiology), Head of Hamilton
NeuroRestorative Group, McMaster University, 1280 Main Street West HSC 4E, Hamilton, ON L8S 4K1, Canada. E-mail: jiangs@mcmaster.ca
How to cite this article: Feng S, Reddy K, Su CX, Jiang SC. Inhibition and reversal of growth cone collapse in adult sensory neurons by enteric
glia-induced neurotrophic factors. Neuroimmunol Neuroinflammation 2016;3:180-8.
ABSTRACT
Article history: Aim: Previous studies show enteric glia (EG)-conditioned medium promotes neurite
Received: 05-01-2016 outgrowth in adult dorsal root ganglia (DRG) derived sensory neurons. This EG-conditioned
Accepted: 12-07-2016 medium contains various neurotrophic factors, including nerve growth factor (NGF), brain-
Published: 31-08-2016 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
Key words: 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
Enteric glia
growth cone collapse 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
nerve growth factor medium to evaluate the factor’s individual importance in preventing growth cone collapse.
brain-derived neurotrophic factor Results: EG-conditioned medium inhibits and reverses growth cone collapse in adult DRG
glial-derived neurotrophic factor neurons when added either 1 h before or concurrently with SEMA3A. When administered 40
neurotrophin-3
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.
INTRODUCTION damage occurs in 2 phases: the primary and secondary
phase. The primary phase is the membrane shearing
Spinal cord injury (SCI) can result in a complete or partial and axonal tearing caused by mechanical stress.
[1]
loss of sensation and paralysis at and below the site of The secondary phase is the ischemia, apoptosis, and
injury and represents a large burden of disease. SCI necrosis that occurs post-trauma. [2,3] Glial scarring at
[1]
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