title: The inhibitory effects of chondroitin sulfate proteoglycans on oligodendrocytes.
abstract: The formation of the glial scar following a spinal cord injury presents a significant barrier to the regenerative process. It is primarily composed of chondroitin sulfate proteoglycans (CSPGs) that can inhibit axonal sprouting and regeneration. Although the inhibitory effects on neurons are well documented, little is known about their effects on oligodendrocyte progenitor cells (OPCs). In this study, we examined the effects of CSPGs on OPC process outgrowth and differentiation in vitro. The results show that specific CSPGs, in particularly those highly up-regulated following spinal cord injury, inhibit OPC process outgrowth and differentiation, and that treatment with chondroitinase ABC can completely reverse this inhibition. Additionally, treatment with the Rho kinase inhibitor Y-27632 also reverses the observed inhibition, implicating the activation of Rho kinase in the CSPG inhibition of OPC growth. Taken together, these findings demonstrate that the CSPGs found within the glial scar are not only inhibitory to neurons, but also to OPCs. Moreover, this study shows that chondroitinase ABC treatment, having shown promise in promoting axonal regeneration, may also enhance remyelination.
authors.affiliation: Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, New York, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Siebert
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Osterhout
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D019765:Chondroitin ABC Lyase / Q000737:chemistry; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D009186:Myelin Sheath / Q000187:drug effects; D009836:Oligodendroglia / Q000187:drug effects*; D011509:Proteoglycans / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000473:pathology; D013234:Stem Cells; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000577:Amides; D011508:Chondroitin Sulfate Proteoglycans; D004791:Enzyme Inhibitors; D011509:Proteoglycans; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases; D019765:Chondroitin ABC Lyase