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)
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DOI：
10.1016/j.bbi.2006.12.007
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发表时间：
2007-05-01
影响因子：
15.1
通讯作者：
Perry, V. H.
中科院分区：
文献类型：
--
作者：
Cunningham, Colin;Campion, Suzanne;Perry, V. H.
聚肌苷酸：聚胞苷酸（poly I：Q）是一种合成的双链RNA，是Toll样受体-3的配体。该受体参与对病毒感染的先天免疫应答，聚I：C已用于模拟病毒感染的急性期。TLR 3激活对脑功能的影响尚未得到广泛研究。在目前的研究中，我们调查的频谱疾病的行为变化引起的聚I：C在C57 BL/6小鼠和中枢神经系统表达的炎症介质，这可能是基础。Poly I：C在2、6和12 mg/kg剂量下诱导剂量反应性疾病行为，减少自发活动、穴居和体重，并在6 h时引起轻度体温过高。12 mg/kg剂量在随后时间引起显著的体温过低。Remo 400远程遥测系统证明了这种双相温度响应的灵敏测量。无论是1周还是3周后，第二次poly I：C激发后，对poly I：C的行为反应均未显着减弱。IL-6、TNF-α和IFN-β的血浆浓度显著升高，IL-1 P也可检测到。通过定量PCR测定，CNS内的细胞因子合成以IL-6为主，IL-1 β、TNF-α和IFN-β的诱导较少，并且脑内皮处存在明显的环氧合酶-2活化。这些发现表明外周TLR 3刺激的明确CNS效应，并且将在研究正常和病理情况下全身性病毒感染对脑功能的影响方面是有用的。(c)2007爱思唯尔公司All rights reserved.
Poly inosinic:poly cytidylic acid (poly I:Q 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 12mg/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 I or 3 weeks later. Plasma concentrations of IL-6, TNF-alpha and IFN-beta were markedly elevated and IL- I P 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. (c) 2007 Elsevier Inc. All rights reserved.