The Chondroitin Sulfate Proteoglycans Neurocan and Phosphacan Are Expressed by Reactive Astrocytes in the Chronic CNS Glial Scar

Abstract

Chondroitin sulfate proteoglycans (CS-PGs) expressed by reactive astrocytes may contribute to the axon growth-inhibitory environment of the injured CNS. The specific potentially inhibitory CS-PGs present in areas of reactive gliosis, however, have yet to be thoroughly examined. In this study, we used immunohistochemistry, combined immunohistochemistry-in situ hybridization, immunoblot analysis, and reverse transcription-PCR to examine the expression of specific CS-PGs by reactive astrocytes in an in vivo model of reactive gliosis: that is, the glial scar, after cortical injury. Neurocan and phosphacan can be localized to reactive astrocytes 30 d after CNS injury, whereas brevican and versican are not expressed in the chronic glial scar. Neurocan is also expressed by astrocytes in primary cell culture. Relative to the amount present in cultured astrocytes or uninjured cortex, neurocan expression increases significantly in the glial scar resulting from cortical injury, including the re-expression of the neonatal isoform of neurocan. In contrast, phosphacan protein levels are decreased in the glial scar compared with the uninjured brain. Because these CS-PGs are capable of inhibiting neurite outgrowth in vitro, our data suggest that phosphacan and neurocan in areas of reactive gliosis may contribute to axonal regenerative failure after CNS injury.

Inhibiting Glycosaminoglycan Chain Polymerization Decreases the Inhibitory Activity of Astrocyte-Derived Chondroitin Sulfate Proteoglycans

“…Activated astrocytes are the main cell type present in the glial scar. Both in vitro and in vivo, activated astrocytes express neurite outgrowth-inhibitory CSPGs (McKeon et al, 1999;Asher et al, 2000;Davies et al, 2004). This makes them an appropriate target for CSPG biosynthesis inhibitors.…”

Incipient Alzheimer's disease: Microarray correlation analyses reveal major transcriptional and tumor suppressor responses

“…For example, the extensive extracellular matrix (ECM) remodeling and cell adhesion changes observed, presumably mediated largely by astrocytes, are similar to processes seen during astrocyte differentiation or cell-type-specific responses to injury (63)(64)(65). Analogous ECM͞adhesion pathways are also used by peripheral cells to suppress cancer cell invasion and metastasis during oncogenesis (66).…”

Effects of P2Y1 receptor on glial fibrillary acidic protein and glial cell line-derived neurotrophic factor production of astrocytes under ischemic condition and the related signaling pathways

“…Activated astrocytes are thought to provide support for damaged neural tissues through several mechanisms, including release of neurotrophic factors [21] . Meanwhile the formation of a glial scar may interfere with neuronal repair or axonal regeneration in the CNS [1,22] . Therefore how to control the astrogliosis and the release of neurotrophic factors attracts our attention.…”