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Control of microglial neurotoxicity by the fractalkine receptor.

Authors
  • Cardona, Astrid E
  • Pioro, Erik P
  • Sasse, Margaret E
  • Kostenko, Volodymyr
  • Cardona, Sandra M
  • Dijkstra, Ineke M
  • Huang, Deren
  • Kidd, Grahame
  • Dombrowski, Stephen
  • Dutta, RanJan
  • Lee, Jar-Chi
  • Cook, Donald N
  • Jung, Steffen
  • Lira, Sergio A
  • Littman, Dan R
  • Ransohoff, Richard M
Type
Published Article
Journal
Nature neuroscience
Publication Date
Jul 01, 2006
Volume
9
Issue
7
Pages
917–924
Identifiers
PMID: 16732273
Source
Medline
License
Unknown

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.

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