Alterations of physiological regulatory networks and neuroendocrinological pathways in a parasitized vertebrate host expressing modified behaviour

表达改变行为的寄生脊椎动物宿主中生理调节网络和神经内分泌途径的改变

• 批准号: RGPIN-2017-05585
• 负责人: AubinHorth, Nadia
• 金额: $ 2.33万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711477
• 关键词: Alterations; physiological; regulatory; networks; neuroendocrinological

Our research program aims to understand the proximate pathways implicated in the modification of the behaviour of a vertebrate host (the threespine stickleback, Gasterosteus aculeatus) when parasitized by an internal tapeworm (Schistocephalus solidus). Sticklebacks act as an intermediate host in this parasite's complex life cycle. Parasitized fish show profoundly changed behaviour: they lose their response to predators, swim closer to the surface, feed at a higher rate under predation risk, and do not school with conspecifics. One of the crucial characteristics of this system is that the parasite grows far from the brain, within the body cavity of its host. The parasite goes through two developmental phases in the fish and these are paralleled by distinct behavioural and physiological phenotypes in the host: a non-infective phase in which the parasite grows to reach up to 90% of the host mass, and an infective stage in which the parasite is ready to move to its final bird host to reproduce. Infected fish show modified behaviour only during the second, infective phase. However, while biologists have fairly well mapped out the changes that occur at the organismal level in the host and when they happen, in comparison we know much less about what changes in the host at the molecular level. Understanding this would help us decipher the causes of the behavioural modifications observed in the host and ultimately to study the evolution of this parasite-host interaction. Based on the behavioural changes observed in the host, we can make predictions about which pathways may be affected. First, variation between individuals and between populations in the behavioural response to predators and in schooling opportunities in healthy sticklebacks has been shown to be associated with the stress response and brain monoamines. Second, daily vertical migrations are often found in fish and are associated with circadian rhythms. Third, it has been proposed that the secreted and excreted products from the parasite (the secretome) are sufficient to activate the immune system in its fish host. However, if and how these physiological regulatory systems are modified in infected fish, whether manipulating them could recreate the behaviour observed in a parasitized host, and if the secretome could alter host behaviour is unknown. We will characterise behaviours and physiological regulatory networks in hosts infected with worms at the non-infective and infective stage, and exposed to the secretome of Schistocephalus. We will measure acute physiological stress response, circadian rhythms and gene expression in the brain (RNA-seq) in specific brain regions. We will test the functional implications of the differences we will find using pharmacological manipulations. Our work will contribute to shed new light on this parasite-host system and on interactions between closely associated species in general.

我们的研究计划旨在了解涉及脊椎动物宿主行为（三杆粘性，gasterosteus aculeatus）的近端途径，当时是由内部tape虫（Schistocephalus solidus）寄生的。在这个寄生虫复杂的生命周期中，粘性充当了中间宿主。寄生的鱼类表现出巨大变化的行为：它们失去了对捕食者的反应，靠近地面游泳，在捕食风险下以更高的速度喂食，并且不与特定的同种上学。该系统的关键特征之一是，寄生虫在其宿主的体腔内生长远离大脑。该寄生虫经历了鱼类中的两个发育阶段，它们与宿主中不同的行为和生理表型平行：一个非感染的阶段，寄生虫生长以达到宿主质量的90％，并且寄生虫可以在其中寄生虫可以移动到最终的鸟类宿主中以重现。感染的鱼仅在第二个感染期显示改变的行为。但是，尽管生物学家已经很好地绘制了宿主生物水平的变化，而当它们发生时，但相比之下，我们对分子水平的宿主的变化知之甚少。理解这将有助于我们破译在宿主中观察到的行为修改的原因，并最终研究这种寄生虫 - 宿主相互作用的演变。基于主机中观察到的行为变化，我们可以对可能受到哪些途径的影响做出预测。首先，个人与人群之间对捕食者的行为反应以及健康粘性的教学机会的差异已被证明与压力反应和脑部单胺有关。其次，每天的垂直迁移通常在鱼类中发现，并且与昼夜节律有关。第三，已经提出，寄生虫（分泌组）的分泌和排泄产品足以激活其鱼类宿主中的免疫系统。但是，如果以及如何在感染鱼类中修改这些生理调节系统，是否可以操纵它们可以重现在寄生的宿主中观察到的行为，并且分泌组是否可以改变宿主行为是未知的。我们将表征在不感染和感染阶段感染蠕虫的宿主中的行为和生理调节网络，并暴露于Schistocephalus的分泌群体中。我们将测量特定大脑区域中大脑（RNA-SEQ）中急性生理压力反应，昼夜节律和基因表达。我们将测试使用药理学操纵将发现的差异的功能含义。我们的工作将有助于对这个寄生虫宿主系统以及一般相关物种之间的相互作用的新启示。