Control of microglial neurotoxicity by the fractalkine receptor

AE Cardona, EP Pioro, ME Sasse, V Kostenko… - Nature …, 2006 - nature.com
AE Cardona, EP Pioro, ME Sasse, V Kostenko, SM Cardona, IM Dijkstra, DR Huang, G Kidd
Nature neuroscience, 2006nature.com
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+ …
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.
nature.com