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Regulation of microglial proliferation during chronic neurodegeneration

Regulation of microglial proliferation during chronic neurodegeneration
Regulation of microglial proliferation during chronic neurodegeneration
An important component of chronic neurodegenerative diseases is the generation of an innate inflammatory response within the CNS. Microglial and astroglial cells play a key role in the development and maintenance of this inflammatory response, showing enhanced proliferation and activation. We studied the time course and regulation of microglial proliferation, using a mouse model of prion disease. Our results show that the proliferation of resident microglial cells accounts for the expansion of the population during the development of the disease. We identify the pathway regulated by the activation of CSF1R and the transcription factors PU.1 and C/EBP? as the molecular regulators of the proliferative response, correlating with the chronic human neurodegenerative conditions variant Creutzfeldt-Jakob disease and Alzheimer's disease. We show that targeting the activity of CSF1R inhibits microglial proliferation and slows neuronal damage and disease progression. Our results demonstrate that microglial proliferation is a major component in the evolution of chronic neurodegeneration, with direct implications for understanding the contribution of the CNS innate immune response to disease progression.
0270-6474
2481-2493
Gómez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Fransen, Nina L.
767c840d-b5d7-4130-b8e5-af2aa4d292e7
Suzzi, Stefano
d666e028-b70c-4c36-92b3-208831ad4bb5
Perry, V Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Gómez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Fransen, Nina L.
767c840d-b5d7-4130-b8e5-af2aa4d292e7
Suzzi, Stefano
d666e028-b70c-4c36-92b3-208831ad4bb5
Perry, V Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4

Gómez-Nicola, Diego, Fransen, Nina L., Suzzi, Stefano and Perry, V Hugh (2013) Regulation of microglial proliferation during chronic neurodegeneration. Journal of Neuroscience, 33 (6), 2481-2493. (doi:10.1523/JNEUROSCI.4440-12.2013). (PMID:23392676)

Record type: Article

Abstract

An important component of chronic neurodegenerative diseases is the generation of an innate inflammatory response within the CNS. Microglial and astroglial cells play a key role in the development and maintenance of this inflammatory response, showing enhanced proliferation and activation. We studied the time course and regulation of microglial proliferation, using a mouse model of prion disease. Our results show that the proliferation of resident microglial cells accounts for the expansion of the population during the development of the disease. We identify the pathway regulated by the activation of CSF1R and the transcription factors PU.1 and C/EBP? as the molecular regulators of the proliferative response, correlating with the chronic human neurodegenerative conditions variant Creutzfeldt-Jakob disease and Alzheimer's disease. We show that targeting the activity of CSF1R inhibits microglial proliferation and slows neuronal damage and disease progression. Our results demonstrate that microglial proliferation is a major component in the evolution of chronic neurodegeneration, with direct implications for understanding the contribution of the CNS innate immune response to disease progression.

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Accepted/In Press date: 11 December 2012
Published date: 6 February 2013
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 348271
URI: https://eprints.soton.ac.uk/id/eprint/348271
ISSN: 0270-6474
PURE UUID: 9112d56c-5385-47cd-9ec6-76c843893454
ORCID for Diego Gómez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

Catalogue record

Date deposited: 11 Feb 2013 12:09
Last modified: 13 Dec 2018 12:32

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