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The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic double-stranded RNA (poly I:C)

The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic double-stranded RNA (poly I:C)
The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic double-stranded RNA (poly I:C)
Poly inosinic:poly cytidylic acid (poly I:C) is a synthetic double-stranded RNA and is a ligand for the Toll like receptor-3. This receptor is involved in the innate immune response to viral infection and poly I:C has been used to mimic the acute phase of a viral infection. The effects of TLR3 activation on brain function have not been widely studied. In the current study we investigate the spectrum of sickness behavioural changes induced by poly I:C in C57BL/6 mice and the CNS expression of inflammatory mediators that may underlie this. Poly I:C, at doses of 2, 6 and 12 mg/kg, induced a dose–responsive sickness behaviour, decreasing locomotor activity, burrowing and body weight, and caused a mild hyperthermia at 6 h. The 12 mg/kg dose caused significant hypothermia at later times. The Remo400 remote Telemetry system proved a sensitive measure of this biphasic temperature response. The behavioural responses to poly I:C were not significantly blunted upon a second poly I:C challenge either 1 or 3 weeks later. Plasma concentrations of IL-6, TNF-? and IFN-? were markedly elevated and IL-1? was also detectable. Cytokine synthesis within the CNS, as determined by quantitative PCR, was dominated by IL-6, with lesser inductions of IL-1?, TNF-? and IFN-? and there was a clear activation of cyclooxygenase-2 at the brain endothelium. These findings demonstrate clear CNS effects of peripheral TLR3 stimulation and will be useful in studying aspects of the effects of systemic viral infection on brain function in both normal and pathological situations.
0889-1591
490-502
Cunningham, Colm
3bc1d897-f0f5-4112-abf4-1a10c2e92a6b
Campion, Suzanne
3d67e320-84c4-4cd3-b278-09b0c8a4c040
Teeling, Jessica
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Felton, Leigh
4d3f36b0-faf6-4e32-8f44-a1e6be97e252
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Cunningham, Colm
3bc1d897-f0f5-4112-abf4-1a10c2e92a6b
Campion, Suzanne
3d67e320-84c4-4cd3-b278-09b0c8a4c040
Teeling, Jessica
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Felton, Leigh
4d3f36b0-faf6-4e32-8f44-a1e6be97e252
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4

Cunningham, Colm, Campion, Suzanne, Teeling, Jessica, Felton, Leigh and Perry, V.H. (2007) The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic double-stranded RNA (poly I:C). Brain, Behavior and Immunity, 21 (4), 490-502. (doi:10.1016/j.bbi.2006.12.007).

Record type: Article

Abstract

Poly inosinic:poly cytidylic acid (poly I:C) is a synthetic double-stranded RNA and is a ligand for the Toll like receptor-3. This receptor is involved in the innate immune response to viral infection and poly I:C has been used to mimic the acute phase of a viral infection. The effects of TLR3 activation on brain function have not been widely studied. In the current study we investigate the spectrum of sickness behavioural changes induced by poly I:C in C57BL/6 mice and the CNS expression of inflammatory mediators that may underlie this. Poly I:C, at doses of 2, 6 and 12 mg/kg, induced a dose–responsive sickness behaviour, decreasing locomotor activity, burrowing and body weight, and caused a mild hyperthermia at 6 h. The 12 mg/kg dose caused significant hypothermia at later times. The Remo400 remote Telemetry system proved a sensitive measure of this biphasic temperature response. The behavioural responses to poly I:C were not significantly blunted upon a second poly I:C challenge either 1 or 3 weeks later. Plasma concentrations of IL-6, TNF-? and IFN-? were markedly elevated and IL-1? was also detectable. Cytokine synthesis within the CNS, as determined by quantitative PCR, was dominated by IL-6, with lesser inductions of IL-1?, TNF-? and IFN-? and there was a clear activation of cyclooxygenase-2 at the brain endothelium. These findings demonstrate clear CNS effects of peripheral TLR3 stimulation and will be useful in studying aspects of the effects of systemic viral infection on brain function in both normal and pathological situations.

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Published date: May 2007

Identifiers

Local EPrints ID: 55943
URI: http://eprints.soton.ac.uk/id/eprint/55943
ISSN: 0889-1591
PURE UUID: b880c3b6-bded-48b7-929a-5fb3898dce5f
ORCID for Jessica Teeling: ORCID iD orcid.org/0000-0003-4004-7391

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Date deposited: 08 Aug 2008
Last modified: 16 Mar 2024 03:41

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Contributors

Author: Colm Cunningham
Author: Suzanne Campion
Author: Jessica Teeling ORCID iD
Author: Leigh Felton
Author: V.H. Perry

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