Regulation and function of the stress response in fish

鱼类应激反应的调节和功能

• 批准号: RGPIN-2015-04498
• 负责人: Bernier, Nicholas
• 金额: $ 3.57万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=645317
• 关键词: Regulation; function; stress; response; fish

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.

鱼类已经进化出各种生理机制来科普自然环境的压力，使它们能够生活在广泛的栖息地，并辐射成脊椎动物中最多样化的物种。 然而，导致生境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规模。 在鱼类中，下丘脑-垂体-肾间（HPI）轴在应激时被激活，并在短期内在协调一系列促进生存的广泛而协调的生理反应中起着关键作用。 相反，HPI轴的慢性激活和皮质醇的产生会导致各种负面后果，在关键的发育窗口期间暴露于压力源会影响鱼类对随后环境挑战的反应。 虽然压力反应的精细平衡调节对健康和生存至关重要，但对以特定方式调节HPI轴的特定机制知之甚少。 我实验室的研究重点是了解负责HPI轴调节的机制，以及早期环境压力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鳟鱼的独特属性，将分子机制与整体结果相结合，本研究的目标是：1）确定神经肽促肾上腺皮质激素释放因子（CRF）在暴露于应激物后的斑马鱼胚胎和成体心脏中是否具有细胞保护作用; 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;第三条确定发育过程中的环境应激源和皮质醇是否对应激反应和空间学习能力产生持续影响成年斑马鱼以及4）确定细胞因子瘦素在低氧虹鳟鱼HPI轴调节中的作用。总的来说，该提案解决了新的问题，环境压力的影响，在塑造成鱼的表型，在发展和成年期的应激介质的细胞保护作用，以及细胞因子在调节HPI轴的功能。 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，扩大我们对介导压力反应的特定机制的了解，并提高我们最大限度地减少或抵消压力对动物的负面影响的能力。 这项研究也有重要的应用动物福利，水产养殖业和机构参与评估人为活动对野生鱼类种群。