Entrapment via synaptic-like connections between NG2 proteoglycan+ cells and dystrophic axons in the lesion plays a role in regeneration failure after spinal cord injury.

Abstract

NG2 is purportedly one of the most growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) produced after spinal cord injury. Nonetheless, once the severed axon tips dieback from the lesion core into the penumbra they closely associate with NG2+ cells. We asked if proteoglycans play a role in this tight cell-cell interaction and whether overadhesion upon these cells might participate in regeneration failure in rodents. Studies using varying ratios of CSPGs and adhesion molecules along with chondroitinase ABC, as well as purified adult cord-derived NG2 glia, demonstrate that CSPGs are involved in entrapping neurons. Once dystrophic axons become stabilized upon NG2+ cells, they form synaptic-like connections both in vitro and in vivo. In NG2 knock-out mice, sensory axons in the dorsal columns dieback further than their control counterparts. When axons are double conditioned to enhance their growth potential, some traverse the lesion core and express reduced amounts of synaptic proteins. Our studies suggest that proteoglycan-mediated entrapment upon NG2+ cells is an additional obstacle to CNS axon regeneration.

• Authors: Angela R Filous, Amanda Tran, C James Howell, Sarah A Busch, Teresa A Evans, William B Stallcup, Shin H Kang, Dwight E Bergles, Seong-il Lee, Joel M Levine, Jerry Silver
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 34 Issue 49 Pg. 16369-84 (Dec 03 2014) ISSN: 1529-2401 [Electronic] United States
• PMID: 25471575 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 the authors 0270-6474/14/3416369-16$15.00/0.

Chemical References

• Antigens
• Chondroitin Sulfate Proteoglycans
• Fibronectins
• Integrin beta1
• Laminin
• Proteoglycans
• chondroitin sulfate proteoglycan 4

Topics

• Animals
• Antigens (genetics, physiology)
• Axons (physiology, ultrastructure)
• Cell Communication (physiology)
• Cell Tracking
• Cells, Cultured
• Chondroitin Sulfate Proteoglycans (physiology)
• Fibronectins (physiology)
• Ganglia, Spinal (physiopathology, ultrastructure)
• Integrin beta1 (physiology)
• Laminin (physiology)
• Mice
• Mice, Knockout
• Nerve Degeneration (physiopathology)
• Nerve Regeneration (physiology)
• Proteoglycans (genetics, physiology)
• Spinal Cord Injuries (physiopathology)
• Synapses (physiology)