Control of microglial neurotoxicity by the fractalkine receptor

Astrid E. Cardona, Erik P. Pioro, Margaret E. Sasse, Volodymyr Kostenko, Sandra M. Cardona, Ineke M. Dijkstra, De Ren Huang, Grahame Kidd, Stephen Dombrowski, Ranjan Dutta, Jar Chi Lee, Donald N. Cook, Steffen Jung, Sergio A. Lira, Dan R. Littman, Richard M. Ransohoff

Research output: Contribution to journalArticlepeer-review

1242 Scopus citations

Abstract

Microglia, the resident inflammatory cells of the CNS, are the only CNS cells that express the fractalkine receptor (CX3CR1). Using three different in vivo models, we show that CX3CR1 deficiency dysregulates microglial responses, resulting in neurotoxicity. Following peripheral lipopolysaccharide injections, Cx3cr1-/- mice showed cell-autonomous microglial neurotoxicity. In a toxic model of Parkinson disease and a transgenic model of amyotrophic lateral sclerosis, Cx3cr1-/- mice showed more extensive neuronal cell loss than Cx3cr1+ littermate controls. Augmenting CX3CR1 signaling may protect against microglial neurotoxicity, whereas CNS penetration by pharmaceutical CX3CR1 antagonists could increase neuronal vulnerability.

Original languageEnglish
Pages (from-to)917-924
Number of pages8
JournalNature Neuroscience
Volume9
Issue number7
DOIs
StatePublished - Jul 2006

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