CS-4,6 is differentially upregulated in glial scar and is a potent inhibitor of neurite extension

Mol Cell Neurosci. 2005 Aug;29(4):545-58. doi: 10.1016/j.mcn.2005.04.006.

Abstract

The precise contribution of different CS-GAGs to CSPG-mediated inhibition of axonal growth after CNS injury is unknown. Quantification of the CS-GAGs in uninjured and injured brain (scar tissue) using fluorophore-assisted carbohydrate electrophoresis (FACE) demonstrated that the dominant CS-GAG in the uninjured brain is CS-4 whereas, in glial scar, CS-2, CS-6, and CS-4,6 were over-expressed. To determine if the pattern of sulfation influenced neurite extension, we compared the effects of CS-GAGs with dominant CS-4, CS-6, or CS-4,6 sulfation to intact CSPG (aggrecan), chondroitin (CS-0), and hyaluronan on chick DRG neurite outgrowth. We report that CS-4,6 GAG, one of the upregulated CS-GAGs in astroglial scar, is potently inhibitory and is comparable to intact aggrecan, a CSPG with known inhibitory properties. Thus, a specific CS-GAG that is differentially over-expressed in astroglial scar is a potent inhibitor of neurite extension. These results may influence the design of more specific strategies to enhance CNS regeneration after injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aggrecans
  • Animals
  • Brain Injuries / metabolism
  • Brain Injuries / physiopathology
  • Chick Embryo
  • Chondroitin / metabolism
  • Chondroitin Sulfates / metabolism*
  • Cicatrix / metabolism*
  • Cicatrix / physiopathology
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Gliosis / metabolism*
  • Gliosis / physiopathology
  • Growth Cones / metabolism
  • Growth Inhibitors / metabolism*
  • Hyaluronic Acid / metabolism
  • Lectins, C-Type / metabolism
  • Neurites / metabolism*
  • Proteoglycans / metabolism
  • Rats
  • Sulfates / metabolism
  • Up-Regulation / physiology

Substances

  • Acan protein, rat
  • Aggrecans
  • Extracellular Matrix Proteins
  • Growth Inhibitors
  • Lectins, C-Type
  • Proteoglycans
  • Sulfates
  • chondroitin 4,6-disulfate
  • chondroitin sulfate glycosaminoglycan
  • Hyaluronic Acid
  • Chondroitin
  • Chondroitin Sulfates