Regulation and function of the stress response in fish

鱼类已经进化出各种生理机制来应对自然环境的压力，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。然而，导致栖息地退化和气候变化加速的人类活动正在降低环境的可预测性，并增加环境压力源的频率和强度。在鱼类中，下丘脑-垂体-肾间轴（HPI）在对压力源的反应中被激活，并在短期内在协调促进生存的一系列广泛而协调的生理反应中发挥关键作用。相反，HPI轴的慢性激活和皮质醇的产生会导致各种各样的负面后果，在关键的发育窗口暴露于压力源会影响鱼对随后环境挑战的反应。尽管应激反应的精细平衡调节对健康和生存至关重要，但相对而言，人们对以特定环境方式调节HPI轴的具体机制知之甚少。我实验室的研究重点是了解HPI轴的调节机制，以及早期环境压力因素影响鱼类对后续挑战的反应的方法。利用斑马鱼作为发育模型和虹鳟鱼的独特属性，将分子机制与整个生物体的结果结合起来，本提案的目标是：1)确定神经肽促肾上腺皮质激素释放因子（CRF）是否在应激源暴露后的斑马鱼胚胎和成年心脏中具有细胞保护作用；2)评估成年斑马鱼皮质醇、神经发生、认知能力和环境复杂性之间的关系；3)研究环境应激源和发育过程中的皮质醇对成年斑马鱼应激反应和空间学习能力的影响是否具有持续性；4)确定细胞因子瘦素在缺氧虹鳟鱼HPI轴调控中的作用。总的来说，该提案解决了关于环境应激源在形成成年鱼表型中的影响、应激介质在发育和成年期间的细胞保护作用以及细胞因子在调节HPI轴中的功能的新问题。因此，这项研究将进一步加深我们对环境压力源的短期和长期影响的理解，拓宽我们对调节压力反应的具体机制的认识，并增强我们减少或抵消动物压力负面影响的能力。这项研究对动物福利、水产养殖业和参与评估对野生鱼类种群的人为活动的机构也有重要的应用。

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.