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Microglial Cx3cr1 knockout reduces prion disease incubation time in mice
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 b...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998043/ https://www.ncbi.nlm.nih.gov/pubmed/24655482 http://dx.doi.org/10.1186/1471-2202-15-44 |
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author | Grizenkova, Julia Akhtar, Shaheen Brandner, Sebastian Collinge, John Lloyd, Sarah E |
author_facet | Grizenkova, Julia Akhtar, Shaheen Brandner, Sebastian Collinge, John Lloyd, Sarah E |
author_sort | Grizenkova, Julia |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3998043 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39980432014-04-25 Microglial Cx3cr1 knockout reduces prion disease incubation time in mice Grizenkova, Julia Akhtar, Shaheen Brandner, Sebastian Collinge, John Lloyd, Sarah E BMC Neurosci Research Article 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. BioMed Central 2014-03-21 /pmc/articles/PMC3998043/ /pubmed/24655482 http://dx.doi.org/10.1186/1471-2202-15-44 Text en Copyright © 2014 Grizenkova et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Grizenkova, Julia Akhtar, Shaheen Brandner, Sebastian Collinge, John Lloyd, Sarah E Microglial Cx3cr1 knockout reduces prion disease incubation time in mice |
title | Microglial Cx3cr1 knockout reduces prion disease incubation time in mice |
title_full | Microglial Cx3cr1 knockout reduces prion disease incubation time in mice |
title_fullStr | Microglial Cx3cr1 knockout reduces prion disease incubation time in mice |
title_full_unstemmed | Microglial Cx3cr1 knockout reduces prion disease incubation time in mice |
title_short | Microglial Cx3cr1 knockout reduces prion disease incubation time in mice |
title_sort | microglial cx3cr1 knockout reduces prion disease incubation time in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998043/ https://www.ncbi.nlm.nih.gov/pubmed/24655482 http://dx.doi.org/10.1186/1471-2202-15-44 |
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