Blockade of A2A adenosine receptors prevents basic fibroblast growth factor-induced reactive astrogliosis in rat striatal primary astrocytes

Roberta Brambilla, Lorenzo Cottini, Marta Fumagalli, Stefania Ceruti, Maria P. Abbracchio

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

Previous literature data show that blockade of A2A adenosine receptors via selective antagonists induces protection in various models of neurodegenerative diseases. The mechanisms underlying this effect are still largely unknown. Since it is known that excessive reactive astrogliosis is a factor contributing to cell death in diseases characterized by neurodegenerative events, the present study has been aimed at determining whether selective A2A receptor antagonists can counteract the formation of reactive astrocytes induced in vitro by basic fibroblast growth factor (bFGF), a typical trigger of this reaction. Exposure of primary rat striatal astrocytes to the selective A2A antagonist SCH58261 resulted in concentration-dependent abolition of BFGF induction of astrogliosis in vitro. This effect could also be reproduced with the chemically unrelated A2A antagonist KW-6002. The direct activation of A2A adenosine receptors by selective receptor agonists was not sufficient per se to induce astrogliosis, suggesting that the A2A receptor needs to act in concert with other bFGF-induced genes to trigger the formation of reactive astrocytes. These results provide a mechanism at the basis of the neuroprotection induced by A2A receptor antagonists in models of brain damage and highlight this adenosine receptor subtype as a novel target for the pharmacological modulation of the gliotic reaction. Ζ 2003 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)190-194
Number of pages5
JournalGlia
Volume43
Issue number2
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Keywords

  • A adenosine receptor
  • Brain inflammation
  • Reactive astrogliosis

ASJC Scopus subject areas

  • Immunology

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