Article abstract


Nature Neuroscience 9, 917 - 924 (2006)
Published online: 18 June 2006 | Corrected online: 18 June 2006 | doi:10.1038/nn1715

Control of microglial neurotoxicity by the fractalkine receptor

Astrid E Cardona1, Erik P Pioro1, Margaret E Sasse1, Volodymyr Kostenko1, Sandra M Cardona1, Ineke M Dijkstra1, DeRen Huang1, Grahame Kidd1, Stephen Dombrowski2, RanJan Dutta1, Jar-Chi Lee3, Donald N Cook4, Steffen Jung5,6, Sergio A Lira7, Dan R Littman6 & Richard M Ransohoff1


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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  1. Neuroinflammation Research Center and Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
  2. Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio 44195, USA.
  3. Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio 44195, USA.
  4. National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
  5. Department of Immunology, Weizman Institute of Science, Rehovot 76100, Israel.
  6. Howard Hughes Medical Institute and Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA.
  7. Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, USA.

Correspondence to: Richard M Ransohoff1 e-mail: ransohr@ccf.org

* replaced figure

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