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Updated: Jul 16, 2026
Induction of Maternal Immune Activation in Mice at Mid-gestation Stage with Viral Mimic Poly(I:C)
Published on: March 25, 2016
The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic
Colm Cunningham1, Suzanne Campion, Jessica Teeling
1Department of Biochemistry, Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland. colm.cunningham@tcd.ie
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 6h. 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-alpha and IFN-beta were markedly elevated and IL-1 beta was also detectable. Cytokine synthesis within the CNS, as determined by quantitative PCR, was dominated by IL-6, with lesser inductions of IL-1 beta, TNF-alpha and IFN-beta 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.
Insights
Poly inosinic:poly cytidylic acid (poly I:C) activates Toll-like receptor 3, causing sickness behaviors and central nervous system inflammation in mice. These effects mimic viral infections and persist after repeated challenges, highlighting TLR3
Area of Science:
- Neuroimmunology
- Infectious Disease Research
- Molecular Biology
Background:
- Poly inosinic:poly cytidylic acid (poly I:C), a synthetic double-stranded RNA, activates Toll-like receptor 3 (TLR3).
- TLR3 is crucial for innate immune responses to viral infections.
- The impact of TLR3 activation on brain function remains underexplored.
Purpose of the Study:
- To investigate sickness behaviors induced by poly I:C in C57BL/6 mice.
- To examine central nervous system (CNS) inflammatory mediator expression following poly I:C administration.
- To understand the role of peripheral TLR3 stimulation in brain function.
Main Methods:
- Administration of varying doses of poly I:C (2, 6, 12 mg/kg) to mice.
- Assessment of behavioral changes including locomotor activity, burrowing, and body weight.
- Monitoring of body temperature using the Remo400 remote Telemetry system.
- Measurement of plasma and CNS cytokine levels (IL-6, TNF-alpha, IFN-beta, IL-1 beta) via quantitative PCR.
- Evaluation of cyclooxygenase-2 activation in brain endothelium.
Main Results:
- Poly I:C induced dose-dependent sickness behaviors and biphasic temperature responses (hyperthermia followed by hypothermia).
- Behavioral responses were not significantly reduced after repeated poly I:C challenges.
- Elevated plasma cytokines (IL-6, TNF-alpha, IFN-beta) and detectable IL-1 beta were observed.
- CNS cytokine expression was dominated by IL-6, with significant induction of IL-1 beta, TNF-alpha, and IFN-beta, alongside cyclooxygenase-2 activation.
Conclusions:
- Peripheral TLR3 stimulation by poly I:C triggers significant sickness behaviors and CNS inflammatory responses in mice.
- These findings provide insights into the neuroinflammatory consequences of viral infections.
- The study demonstrates the utility of poly I:C as a model for studying viral infection effects on brain function.
