Regulation and function of the stress response in fish

鱼类进化了各种生理机制来应对自然环境压力，使它们能够生活在广泛的栖息地，并辐射到脊椎动物中最多样化的物种群体。然而，导致栖息地退化和气候加速变化的人类活动正在降低环境的可预测性，并增加环境应激源的频率和程度。在鱼类中，下丘脑-垂体-肾间轴(HPI)是对应激源的反应被激活，在短期内在协调一系列广泛和协调的生理反应以促进生存方面发挥着关键作用。相比之下，HPI轴的慢性激活和皮质醇的产生可能会导致各种负面后果，在关键发育窗口期间暴露于应激源可能会影响鱼类对随后环境挑战的反应。尽管对应激反应的精细平衡调节对健康和生存至关重要，但对以特定背景方式调节HPI轴的具体机制知之甚少。我实验室的研究重点是了解调节HPI轴的机制，以及早期环境应激源影响鱼类对后续挑战的反应的方式。利用斑马鱼作为发育模型和虹鱼独特的属性将分子机制与整个生物体的结果相结合，该建议的目标是1)确定神经肽促肾上腺皮质激素释放因子(CRF)在暴露于应激源后是否对斑马鱼胚胎和成年心脏具有细胞保护作用；2)评估成年斑马鱼皮质醇、神经发生、认知表现和环境复杂性之间的关系；3)确定发育过程中的环境应激源和皮质醇是否对成年斑马鱼的应激反应和空间学习能力具有持久的影响；以及4)确定细胞因子瘦素在调节缺氧彩虹鱼HPI轴中的作用。总体而言，该提案解决了环境应激源对成鱼表型形成的影响、应激介质在发育和成体过程中的细胞保护作用以及细胞因子在调节HPI轴中的功能等新问题。因此，这项研究将加深我们对环境应激源的短期和长期影响的理解，拓宽我们对调节应激反应的具体机制的认识，并增强我们将应激对动物的负面影响降至最低或抵消的能力。这项研究在动物福利、水产养殖业以及参与野生鱼类种群人为活动评估的机构中也有重要的应用。

Fish have evolved various physiological mechanisms to cope with natural environmental stressors enabling them to live in a broad range of habitats as well as to radiate into the most diverse group of species among vertebrates. However, human activities leading to habitat degradation and accelerated climate change are reducing the predictability of the environment, and increasing the frequency and magnitude of environmental stressors. In fish, the hypothalamic-pituitary-interrenal (HPI) axis is activated in response to stressors and in the short term plays a pivotal role in orchestrating a broad and coordinated suite of physiological responses that promote survival. In contrast, chronic activation of the HPI axis and cortisol production can lead to a variety of negative consequences and exposure to stressors during critical developmental windows can influence the responses of fish to subsequent environmental challenges. Although fine-balance regulation of the stress response is essential to health and survival, relatively little is known about the specific mechanisms that regulate the HPI axis in a context-specific manner. Research in my lab is focused on understanding the mechanisms responsible for the regulation of the HPI axis and the means by which early environmental stressors affect the responses of fish to subsequent challenges. Taking advantage of the unique attributes of zebrafish as a developmental model and of rainbow trout to integrate molecular mechanisms with whole-organism outcomes, the goals of this proposal are to 1) determine whether the neuropeptide corticotropin-releasing factor (CRF) has cytoprotective actions in zebrafish embryos and adult hearts following exposure to stressors; 2) assess the relationships between cortisol, neurogenesis, cognitive performance and environmental complexity in adult zebrafish; 3) establish whether environmental stressors and cortisol during development have persistent effects on the stress response and spatial learning abilities of adult zebrafish; and 4) determine the role of the cytokine leptin in the regulation of the HPI axis in hypoxic rainbow trout. Overall, the proposal addresses novel questions about the impact of environmental stressors in shaping the phenotype of adult fish, the cytoprotective roles of stress mediators during development and adulthood, and the function of cytokines in regulating the HPI axis. As such, this research will further our understanding of the short and long term impact of environmental stressors, broaden our knowledge of the specific mechanisms that mediate the stress response, and enhance our ability to minimize or counteract the negative impact of stress in animals. This research also has important applications for animal welfare, the aquaculture industry and for agencies involved in the assessment of anthropogenic activities on wild fish populations.