Expression of C5a receptor in mouse brain: Role in signal transduction and neurodegeneration

H. Osaka, Ann McGinty, U.E. Hoepken, Wanhua Lu, C. Gerard, G.M. Pasinetti

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

In this study we explored the potential role of the complement derived anaphylatoxin C5a and the expression of its receptor in mouse brain. Using in situ hybridization, we found that C5a receptor messenger RNA is expressed in mouse brain. In response to intraventricular kainic acid injection, there was marked increase in the C5a receptor messenger RNA expression, particularly in hippocampal formation and cerebral cortex. C5a ligand-binding autoradiography confirmed the functional expression and elevation of the C5a receptor post-lesioning. The expression of Cia receptor messenger RNA in brain was confirmed by northern blot hybridization of total RNA from neuronal and glial cells in vitiro. Based on these findings we explored the role of C5a in mechanisms of signal transduction in brain cells. Treatment of primary cultures of mouse astrocytes with human recombinant C5a resulted in the activation of mitogen-activated extracellular signal-regulated protein kinase. This response appeared to be mediated by the C5a receptor since astrocyte cultures derived from C5a receptor knockout mice were not responsive to the treatment. Understanding the regulation of C5a receptor in brain and mechanisms by which pro-inflammatory C5a modulates specific signal transduction pathways in brain cells is crucial to studies of inflammatory mechanisms in neurodegeneration. (C) 1998 IBRO. Published by Elsevier Science Ltd.
Original languageEnglish
Pages (from-to)1073-1082
Number of pages10
JournalNeuroscience
Volume88
Issue number4
Publication statusPublished - Feb 1999

ASJC Scopus subject areas

  • Neuroscience(all)

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