The chondroitin sulphate proteoglycan brevican is upregulated by astrocytes after entorhinal cortex lesions in adult rats

Abstract

The chondroitin sulphate proteoglycan brevican is one of the most abundant extracellular matrix molecules in the adult rat brain. It is primarily synthesized by astrocytes and is believed to influence astroglial motility during development and under certain pathological conditions. In order to study a potential role of brevican in the glial reaction after brain injury, its expression was analysed following entorhinal cortex lesion in rats (12 h, 1, 2, 4, 10, 14 and 28 days and 6 months post lesion). In situ hybridization and immunohistochemistry were employed to study brevican mRNA and protein, respectively, in the denervated outer molecular layer of the fascia dentata and at the lesion site. In both regions brevican mRNA was upregulated between 1 and 4 days post lesion. The combination of in situ hybridization with immunohistochemistry for glial fibrillary acidic protein demonstrated that many brevican mRNA-expressing cells are astrocytes. In the denervated zone of the fascia dentata, immunostaining for brevican was increased by 4 days, reached a maximum by 4 weeks and remained detectable up to 6 months post lesion. Electron microscopic immunocytochemistry showed that brevican is a component of the extracellular matrix compartment. At the lesion site a similar time course of brevican upregulation was observed. These data demonstrate that brevican is upregulated in areas of brain damage as well as in areas denervated by a lesion. They suggest a role of brevican in reactive gliosis and are compatible with the hypothesis that brevican is involved in the synaptic reorganization of denervated brain areas.

Relationship between sprouting axons, proteoglycans and glial cells following unilateral nigrostriatal axotomy in the adult rat

“…In addition, NG2 immunoreactivity was associated with blood vessels in the lesion core. Other studies have similarly demonstrated the presence of CSPGs at sites of CNS injury, including NG2 (Levine, 1994), neurocan (McKeon and Buck, 1997), phosphacan (Barker et al, 1996), versican McKeon et al, 1999) and brevican (Jaworski et al, 1995;Haas et al, 1999;Thon et al, 2000). In vitro, and at sites of CNS injury, CSPGs are generally produced by reactive glia: astrocytes are thought to make neurocan and phosphacan while oligodendrocyte precursors make NG2, neurocan, and phosphacan (Maurel et al, 1994;Faissner et al, 1994;Engel et al, 1996;Meyer-Pullitz et al, 1996;Nishiyama et al, 1999;Asher et al, 2000a).…”

The Proteoglycan Brevican Binds to Fibronectin after Proteolytic Cleavage and Promotes Glioma Cell Motility

“…Neurons do not attach well to surfaces coated with brevican and do not extend axons toward a surface containing this chondroitin sulfate proteoglycan (53,54). In vivo, brevican is expressed around the boundaries of the rostral migratory stream (55) and is a major up-regulated component of the glial scar after neural injury (56,57), limiting axonal extension and probably limiting neuroblast and astrocyte motility (53,55). Thus, brevican seems to function in the neural matrix predominantly as a stop signal for motile neural cells or extending neurites.…”

Versican V2 Assembles the Extracellular Matrix Surrounding the Nodes of Ranvier in the CNS

“…Recombinant portions of aggrecan (mAC-IGD: residues 368 -481 and mAC-GAG: 1678 -1896; Swiss-Prot Q61282) and neurocan (mNC-C: residues 645-944; Swiss-Prot P55066) served as antigens for the immunization of guinea pigs. Rabbit antisera against rat brevican (Thon et al, 2000) and TnR (Day et al, 2004) were kind gifts of Takako Sasaki (University of Erlangen, Erlangen, Germany) and Anders Aspberg (University of Lund, Lund, Sweden), respectively.…”