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| Francesca Properzi |
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Brain Repair Centre, University of Cambridge, CB2 2PY Cambridge, UKUK
e-mail: fp218@cam.ac.uk |
Poster Presentation: |
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| THE EXPRESSION OF SPECIFIC CHONDROITIN SULFOTRANSFERASES IN THE CNS AFTER INJURY IS RELATED TO THE INHIBITION OF AXONAL REGENERATION. |
| Francesca Properzi, Richard A. Asher, James W. Fawcett | |
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Brain Repair Centre, University of Cambridge, UK |
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| Chondroitin sulfate proteoglycans (CSPGs) are upregulated in the CNS after injury, specifically around the lesion site where glial scar forms. This structure contains astrocytes, oligodendrocytes precursors (OPCs), microglia and meningeal cells and forms an inhibitory substrate for axon regrowth. CSPGs have been shown to be primarily involved in this neuronal growth inhibition, specifically through their sugar chains. We show that the expression of the chondroitin sulfotransferases (CSSTs), the enzymes sulfating the disaccharide residues of CSPGs, is differently regulated in CNS before and after injury and in the different cell lines involved in the scarring process. The CSSTs known so far belong to three different subtypes adding the sulfate groups in three different positions of the disaccharide unit. They are called C4STs (C4ST-1 and C4ST-2), C6STs (C6ST-1 and C6ST-2) and UST. Semiquantitative RT-PCR results on adult rat brain showed that C6ST-1 and UST mRNAs are selectively up-regulated after a unilateral cortical stab lesion in the area where the glial scar forms. The expression of the other CSST mRNAs remains unchanged. On Neu7 astrocytes, which are a non-permissive substrate for axon growth, due to the overexpression of CSPGs, all CSST mRNAs are expressed at high levels. Interestingly, in A7 astrocytes, which are a good substrate for axon growth the C6ST-1 mRNA is not detectable. The same mRNA is strongly upregulated on astrocytes after treatment with TGFa, which is one of the brain injury-related cytokines. High levels of C6ST-1 mRNA, as well as the other CSST mRNAs, are also found in the OPCs and in meningeal cells, which are both cell types involved in the formation of the glial scar. These data suggest that both the upregulation and the sulfation pattern of CSPGs could be involved in the inhibition of axon regrowth in the CNS.
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