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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744988
• 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脊椎动物宿主（三刺棘鱼，Gasterosteus aculeatus）被体内绦虫（Schistocephalus Solidus）寄生时行为改变所涉及的直接途径。刺鱼在这种寄生虫复杂的生命周期中充当中间宿主。被寄生的鱼的行为发生了深刻的变化：它们失去了对捕食者的反应，游得更靠近水面，在被捕食风险下以更高的速度进食，并且不与同种鱼结群。该系统的关键特征之一是寄生虫生长在远离大脑的宿主体腔内。寄生虫在鱼体内经历两个发育阶段，与宿主中不同的行为和生理表型并行：非感染阶段，寄生虫生长达到宿主质量的 90%；感染阶段，寄生虫准备好转移到最终的鸟类宿主进行繁殖。受感染的鱼仅在第二个感染阶段表现出行为改变。然而，虽然生物学家已经相当清楚地描绘出宿主在有机体水平上发生的变化以及这些变化何时发生，但相比之下，我们对宿主在分子水平上发生的变化知之甚少。了解这一点将有助于我们破译在宿主中观察到的行为改变的原因，并最终研究这种寄生虫与宿主相互作用的进化。根据在宿主中观察到的行为变化，我们可以预测哪些途径可能受到影响。首先，健康刺鱼对捕食者的行为反应和受教育机会的个体之间和群体之间的差异已被证明与压力反应和大脑单胺有关。其次，鱼类经常进行每日垂直迁移，并且与昼夜节律相关。第三，有人提出，寄生虫的分泌和排泄产物（分泌组）足以激活鱼类宿主的免疫系统。然而，这些生理调节系统是否以及如何在受感染的鱼类中发生改变，操纵它们是否可以重现在寄生宿主中观察到的行为，以及分泌组是否可以改变宿主行为，这些都是未知的。我们将描述在非感染和感染阶段感染蠕虫并暴露于裂头虫分泌体的宿主的行为和生理调节网络。我们将测量特定大脑区域的急性生理应激反应、昼夜节律和大脑基因表达 (RNA-seq)。我们将使用药理学操作来测试我们发现的差异的功能含义。我们的工作将有助于为这种寄生虫宿主系统以及密切相关的物种之间的相互作用提供新的线索。