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Open Access Highly Accessed Research article

Microglial Cx3cr1 knockout reduces prion disease incubation time in mice

Julia Grizenkova, Shaheen Akhtar, Sebastian Brandner, John Collinge and Sarah E Lloyd*

Author Affiliations

MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK

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BMC Neuroscience 2014, 15:44  doi:10.1186/1471-2202-15-44

Published: 21 March 2014

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).

Conclusion

Our data suggest a protective role for Cx3cl1/Cx3cr1 cross-talk in prion disease.

Keywords:
Prion disease; Incubation time; Cx3cr1; Microglia; Cytokines; Chemokines