FGF/heparin differentially regulates Schwann cell and olfactory ensheathing cell interactions with astrocytes: a role in astrocytosis

Santos-Silva, A., Fairless, R., Frame, M.C., Montague, P., Smith, G.M., Toft, A., Riddell, J.S. and Barnett, S.C. (2007) FGF/heparin differentially regulates Schwann cell and olfactory ensheathing cell interactions with astrocytes: a role in astrocytosis. Journal of Neuroscience, 27(27), pp. 7154-7167. (doi:10.1523/JNEUROSCI.1184-07.2007)

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Publisher's URL: http://dx.doi.org/10.1523/JNEUROSCI.1184-07.2007

Abstract

After injury, the CNS undergoes an astrocyte stress response characterized by reactive astrocytosis/proliferation, boundary formation, and increased glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycan (CSPG) expression. Previously, we showed that in vitro astrocytes exhibit this stress response when in contact with Schwann cells but not olfactory ensheathing cells (OECs). In this study, we confirm this finding in vivo by demonstrating that astrocytes mingle with OECs but not Schwann cells after injection into normal spinal cord. We show that Schwann cell-conditioned media (SCM) induces proliferation in monocultures of astrocytes and increases CSPG expression in a fibroblast growth factor receptor 1 (FGFR1)-independent manner. However, SCM added to OEC/astrocyte cocultures induces reactive astrocytosis and boundary formation, which, although sensitive to FGFR1 inhibition, was not induced by FGF2 alone. Addition of heparin to OEC/astrocyte cultures induces boundary formation, whereas heparinase or chlorate treatment of Schwann cell/astrocyte cultures reduces it, suggesting that heparan sulfate proteoglycans (HSPGs) are modulating this activity. In vivo, FGF2 and FGFR1 immunoreactivity was increased over grafted OECs and Schwann cells compared with the surrounding tissue, and HSPG immunoreactivity is increased over reactive astrocytes bordering the Schwann cell graft. These data suggest that components of the astrocyte stress response, including boundary formation, astrocyte hypertrophy, and GFAP expression, are mediated by an FGF family member, whereas proliferation and CSPG expression are not. Furthermore, after cell transplantation, HSPGs may be important for mediating the stress response in astrocytes via FGF2. Identification of factors secreted by Schwann cells that induce this negative response in astrocytes would further our ability to manipulate the inhibitory environment induced after injury to promote regeneration.

Item Type:Articles
Keywords:Glia, reactive astrocytes, FGF2, heparin, rat, Schwann cell.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Montague, Dr Paul and Barnett, Professor Susan and Riddell, Dr John and Toft, Mr Andrew
Authors: Santos-Silva, A., Fairless, R., Frame, M.C., Montague, P., Smith, G.M., Toft, A., Riddell, J.S., and Barnett, S.C.
Subjects:Q Science > QP Physiology
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Neuroscience
Publisher:The Society for Neuroscience
ISSN:0270-6474
Copyright Holders:Copyright © 2007 The Society for Neuroscience
First Published:First published in Journal of Neuroscience 27(27):7154-7167
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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