Brain pathways for neurally-mediated fever: from vagal afferent to sympathetic output to brown adipose tissue via brain

神经介导发烧的大脑通路：从迷走神经传入到交感神经输出，通过大脑到棕色脂肪组织

• 批准号: nhmrc : 426716
• 负责人: Dr Youichirou Ootsuka
• 金额: $ 27.02万
• 依托单位: Flinders University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/brain-pathways-neurally-tissue-brain/99378
• 关键词: Brain; pathways; neurally; mediated; fever

Fever is one of the immune defence reactions to the invasion of microorganisms such as bacteria and viruses. Fever reflects increased heat production and decreased heat loss. Systems regulating heat production and heat loss are under brain control. To trigger fever, the immune system must alert the brain to the presence of infection. The general view of how the alerting system triggers fever is that it develops in sequential steps. Macrophages ingest microorganisms, and then regulatory proteins (cytokines) are released. The cytokines enter the blood stream and are transported to the brain. Recently, the existence of another signalling pathway has been demonstrated. The pathway is via a special peripheral sensory nerve, the abdominal vagal sensory nerve. However, special neural pathways in the brain have not yet been clarified, even though several neural relay stations have been proposed. To elucidate neural pathways transmitting information of infection to the brain, both input and output of the pathway need to be specified. Specific outputs other than body temperature have not been determined, so far. I have recently developed a new reflex model, in which I focus on sympathetic nerves supplying the specialised fat tissue as an output as well as the vagus sensory nerve as an input. The fat tissue, brown adipose tissue (BAT), generates heat. When the vagus sensory nerve is stimulated electrically, BAT sympathetic nerve is activated. We were very exited when we discovered the potency of the combination in our rat model. We are now ready to elucidate brain pathways for neurally-mediated fever, using our new reflex model. Signalling to the brain via the nervous system is faster than via the blood stream, and thus must be very important for the earliest phase of fever. Understanding the neural pathways by which the brain perceives peripheral infection and triggers fever may promote beneficial aspects of the acute-phase immune reaction.

发烧是对细菌和病毒等微生物入侵的免疫防御反应之一。发热反映了热量产生增加和热量损失减少。调节热量产生和损失的系统由大脑控制。为了引发发烧，免疫系统必须警告大脑感染的存在。关于警报系统如何触发发烧的一般观点是，它是按顺序发展的。巨噬细胞吞噬微生物，然后释放调节蛋白（细胞因子）。细胞因子进入血流并被运送到大脑。最近，另一个信号通路的存在已被证明。该通路是通过一种特殊的外周感觉神经，腹部迷走神经感觉神经。然而，大脑中的特殊神经通路尚未澄清，尽管已经提出了几个神经中继站。为了阐明将感染信息传递到大脑的神经通路，需要指定通路的输入和输出。到目前为止，尚未确定体温以外的具体输出。我最近开发了一个新的反射模型，其中我专注于交感神经提供专门的脂肪组织作为输出以及迷走感觉神经作为输入。脂肪组织，棕色脂肪组织（BAT），产生热量。当迷走感觉神经被电刺激时，BAT交感神经被激活。当我们在我们的大鼠模型中发现这种组合的效力时，我们非常兴奋。我们现在准备使用我们的新反射模型来阐明神经介导的发热的大脑通路。通过神经系统传递到大脑的信号比通过血流传递的信号更快，因此对发烧的早期阶段非常重要。了解大脑感知外周感染并引发发热的神经通路可能会促进急性期免疫反应的有益方面。