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Comparison of inflammatory and acute-phase responses in the brain and peripheral organs of the ME7 model of prion disease

Comparison of inflammatory and acute-phase responses in the brain and peripheral organs of the ME7 model of prion disease
Comparison of inflammatory and acute-phase responses in the brain and peripheral organs of the ME7 model of prion disease
Chronic neurodegenerative diseases such as prion disease and Alzheimer's disease (AD) are reported to be associated with microglial activation and increased brain and serum cytokines and acute-phase proteins (APPs). Unlike AD, prion disease is also associated with a peripheral component in that the presumed causative agent, PrPSc, also accumulates in the spleen and other lymphoreticular organs. It is unclear whether the reported systemic acute-phase response represents a systemic inflammatory response to prion disease or merely reflects central nervous system (CNS) inflammation. For this study, we investigated whether intracerebrally initiated prion disease (ME7 model) provokes splenic, hepatic, or brain inflammatory and acute-phase responses. We detected no significant elevation of proinflammatory cytokines or activation of macrophages in the spleens of these animals, despite clear PrPSc deposition. Similarly, at 19 weeks we detected no significant elevation of transcripts for the APPs serum amyloid A, complement C3, pentraxin 3, and alpha2-antiplasmin in the liver, despite CNS neurodegeneration and splenic PrPSc deposition at this time. However, despite the low CNS expression levels of proinflammatory cytokines, there was robust expression of these APPs in degenerating brains. These findings suggest that PrPSc is not a stimulus for splenic macrophages and that neither peripheral PrPSc deposition nor CNS neurodegeneration is sufficient to produce a systemic acute-phase response. We also propose that serum cytokine and APP measurements are not useful during preclinical disease. Possible consequences of the clear chronic elevation of APPs in the CNS are discussed.
0022-538X
5174-5184
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Wilcockson, DC.
a46264fd-be5e-41ab-8761-4eefe5cf3a8c
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Perry, VH.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Wilcockson, DC.
a46264fd-be5e-41ab-8761-4eefe5cf3a8c
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Perry, VH.
8f29d36a-8e1f-4082-8700-09483bbaeae4

Cunningham, C., Wilcockson, DC., Boche, D. and Perry, VH. (2005) Comparison of inflammatory and acute-phase responses in the brain and peripheral organs of the ME7 model of prion disease. Journal of Virology, 79 (8), 5174-5184. (doi:10.1128/JVI.79.8.5174-5184.2005).

Record type: Article

Abstract

Chronic neurodegenerative diseases such as prion disease and Alzheimer's disease (AD) are reported to be associated with microglial activation and increased brain and serum cytokines and acute-phase proteins (APPs). Unlike AD, prion disease is also associated with a peripheral component in that the presumed causative agent, PrPSc, also accumulates in the spleen and other lymphoreticular organs. It is unclear whether the reported systemic acute-phase response represents a systemic inflammatory response to prion disease or merely reflects central nervous system (CNS) inflammation. For this study, we investigated whether intracerebrally initiated prion disease (ME7 model) provokes splenic, hepatic, or brain inflammatory and acute-phase responses. We detected no significant elevation of proinflammatory cytokines or activation of macrophages in the spleens of these animals, despite clear PrPSc deposition. Similarly, at 19 weeks we detected no significant elevation of transcripts for the APPs serum amyloid A, complement C3, pentraxin 3, and alpha2-antiplasmin in the liver, despite CNS neurodegeneration and splenic PrPSc deposition at this time. However, despite the low CNS expression levels of proinflammatory cytokines, there was robust expression of these APPs in degenerating brains. These findings suggest that PrPSc is not a stimulus for splenic macrophages and that neither peripheral PrPSc deposition nor CNS neurodegeneration is sufficient to produce a systemic acute-phase response. We also propose that serum cytokine and APP measurements are not useful during preclinical disease. Possible consequences of the clear chronic elevation of APPs in the CNS are discussed.

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Published date: April 2005

Identifiers

Local EPrints ID: 27557
URI: https://eprints.soton.ac.uk/id/eprint/27557
ISSN: 0022-538X
PURE UUID: f99b14f8-9793-4991-b63d-1d240e38433b
ORCID for D. Boche: ORCID iD orcid.org/0000-0002-5884-130X

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Date deposited: 25 Apr 2006
Last modified: 06 Jun 2018 12:52

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Contributors

Author: C. Cunningham
Author: DC. Wilcockson
Author: D. Boche ORCID iD
Author: VH. Perry

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