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MCP-1 and murine prion disease: separation of early behavioural dysfunction from overt clinical disease

MCP-1 and murine prion disease: separation of early behavioural dysfunction from overt clinical disease
MCP-1 and murine prion disease: separation of early behavioural dysfunction from overt clinical disease
Prion diseases are chronic, fatal neurodegenerative conditions of the CNS. We have investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the ME7 model of murine prion disease. MCP-1 expression increased in the CNS throughout disease progression and was positively correlated with microglial activation. We subsequently compared the inflammatory response, pathology and behavioural changes in wild-type (wt) mice and MCP-1 knockout mice (MCP-1?/?) inoculated with ME7. Late-stage clinical signs were delayed by 4 weeks in MCP-1?/? mice, and survival time increased by 2–3 weeks. By contrast, early changes in affective behaviours and locomotor activity were not delayed in onset. There was also no difference in microglial activation or neuronal death in the hippocampus and thalamus of wt mice and MCP-1?/? mice. These results highlight an important dissociation between prolonged survival, early behavioural dysfunction and hippocampal/thalamic pathology when considering therapeutic intervention for human prion diseases and other chronic neurodegenerative conditions
prion disease, scrapie, me7, behaviour, microgliam, chemokine, mcp-1, neurodegeneration, survival
0969-9961
283-295
Felton, LM.
658d9238-436e-4c9d-a7ea-239efd076f2e
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Rankine, EL.
d52ddab5-b12b-492f-9eab-08d6db261513
Waters, S.
7eefd97d-ab0d-437b-8935-deee6b3a85f8
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Perry, VH.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Felton, LM.
658d9238-436e-4c9d-a7ea-239efd076f2e
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Rankine, EL.
d52ddab5-b12b-492f-9eab-08d6db261513
Waters, S.
7eefd97d-ab0d-437b-8935-deee6b3a85f8
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Perry, VH.
8f29d36a-8e1f-4082-8700-09483bbaeae4

Felton, LM., Cunningham, C., Rankine, EL., Waters, S., Boche, D. and Perry, VH. (2005) MCP-1 and murine prion disease: separation of early behavioural dysfunction from overt clinical disease. Neurobiology of Disease, 20 (2), 283-295. (doi:10.1016/j.nbd.2005.03.008).

Record type: Article

Abstract

Prion diseases are chronic, fatal neurodegenerative conditions of the CNS. We have investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the ME7 model of murine prion disease. MCP-1 expression increased in the CNS throughout disease progression and was positively correlated with microglial activation. We subsequently compared the inflammatory response, pathology and behavioural changes in wild-type (wt) mice and MCP-1 knockout mice (MCP-1?/?) inoculated with ME7. Late-stage clinical signs were delayed by 4 weeks in MCP-1?/? mice, and survival time increased by 2–3 weeks. By contrast, early changes in affective behaviours and locomotor activity were not delayed in onset. There was also no difference in microglial activation or neuronal death in the hippocampus and thalamus of wt mice and MCP-1?/? mice. These results highlight an important dissociation between prolonged survival, early behavioural dysfunction and hippocampal/thalamic pathology when considering therapeutic intervention for human prion diseases and other chronic neurodegenerative conditions

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More information

Published date: November 2005
Keywords: prion disease, scrapie, me7, behaviour, microgliam, chemokine, mcp-1, neurodegeneration, survival

Identifiers

Local EPrints ID: 27572
URI: https://eprints.soton.ac.uk/id/eprint/27572
ISSN: 0969-9961
PURE UUID: a5f8d5e6-c7d3-4b36-a643-215a3eb71e4c
ORCID for D. Boche: ORCID iD orcid.org/0000-0002-5884-130X

Catalogue record

Date deposited: 25 Apr 2006
Last modified: 20 Jul 2019 01:07

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