Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars.

Abstract

Following injury to the adult CNS, the expression of a number of extracellular matrix molecules increases in regions of reactive gliosis. This glial matrix includes certain chondroitin sulfate proteoglycans (CS-PGs) which have been correlated with an inhibition of axon outgrowth. In order to test the influence of glial associated CS-PGs on neurite elongation directly, we sought to determine whether enzymatic modification of injury-induced CS-PGs could enhance neurite outgrowth across the surface of intact glial scars formed in vivo after implanting nitrocellulose filters into the cortex of adult rats. This gliotic tissue was subsequently explanted in vitro and used as a substrate for growing embryonic retinal neurons. Treatment of adult explants with chondroitinase ABC led to a significant increase in mean neurite length over the scar surface. Heparitinase treatment caused a much smaller, although significant, increase in neurite outgrowth. This suggested that more than one type of PG was present or that a single PG with both CS and HS side chains was upregulated. Western analysis revealed that a PG(s) with a core protein between 180 and 400 kDa was found to be relatively more abundant in areas of reactive gliosis induced to form in adult rather than neonatal animals. Simultaneous treatment of adult glial scars with chondroitinase and antibodies to the beta 1, beta 2 chain of laminin partially reversed the growth-enhancing effect of enzymatic digestion alone. These data demonstrate that the increase in neurite outgrowth along the surface of reactive astrocytes following enzymatic modification of injury-induced PGs was due, in part, to the presence of laminin. Thus, in this model of gliosis, particular PGs may act as inhibitors of neurite outgrowth by attenuating the potential for axon elongation that could occur due to the concomitant expression of growth-promoting molecules in regions of reactive gliosis.

• Authors: R J McKeon, A Höke, J Silver
• Journal: Experimental neurology (Exp Neurol) Vol. 136 Issue 1 Pg. 32-43 (Nov 1995) ISSN: 0014-4886 [Print] United States
• PMID: 7589332 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies
• Proteoglycans

Topics

• Animals
• Antibodies (immunology)
• Astrocytes (physiology)
• Axons (physiology)
• Blotting, Western
• Enzyme Activation
• Extracellular Matrix (physiology)
• Gliosis (metabolism)
• Immunohistochemistry
• Neurites (physiology)
• Proteoglycans (biosynthesis)
• Rats
• Rats, Sprague-Dawley