title: Microglial Cx3cr1 knockout reduces prion disease incubation time in mice.
abstract: BACKGROUND
  Microglia are resident mononuclear phagocytes of the brain that become activated in response to insults including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and prion disease. In the central nervous system the chemokine Cx3cl1 (Fractalkine) is expressed by neurons and its exclusive receptor Cx3cr1 is expressed solely on microglia. Cx3cl1/Cx3cr1 signalling is thought to maintain microglia in their resting state and disrupting this equilibrium may allow microglia to become activated. In prion disease, microglial proliferation has been suggested to contribute to overall disease progression, however, in different mouse models of neurodegeneration, loss of Cx3cr1 has been shown to either worsen or improve the phenotype depending on the paradigm.
  
  
  RESULTS
  To investigate the role of Cx3cl1/Cx3cr1 signalling in prion disease we infected Cx3cr1 null mice with three different strains of prions. Following challenge with Chandler/RML, ME7 and MRC2 prion strains, Cx3cr1 knockout mice showed highly significant reductions in incubation time. No differences were seen in the pattern and localisation of activated microglia in the brain or in the mRNA expression levels of chemokines/cytokines (Cxcl10, Il-12b, Il-1b, Arg-1 and Cxc3l1).
  
  
  CONCLUSIONS
  Our data suggest a protective role for Cx3cl1/Cx3cr1 cross-talk in prion disease.
authors.forename: Julia
authors.initials: J
authors.lastname: Grizenkova
authors.forename: Shaheen
authors.initials: S
authors.lastname: Akhtar
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandner
authors.forename: John
authors.initials: J
authors.lastname: Collinge
authors.affiliation: MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK. s.lloyd@prion.ucl.ac.uk.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Lloyd
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D055256:Infectious Disease Incubation Period; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*
chemical_list: D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine