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Environmental Stressors and the Neuroendocrine Stress Response in Zebrafish: Consequences and Cytoprotective Mechanisms

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Title: Environmental Stressors and the Neuroendocrine Stress Response in Zebrafish: Consequences and Cytoprotective Mechanisms
Author: Williams, Tegan
Department: Department of Integrative Biology
Program: Integrative Biology
Advisor: Bernier, Nicholas
Abstract: This thesis focuses on the effects of environmental stressors during early life development and the impact of these stressors on the function of the neuroendocrine stress response. Additionally, this thesis describes novel cytoprotective functions of CRF-peptides, using zebrafish as a model. Larvae exposed to high environmental ammonia (HEA) had elevated cortisol levels and increased expression of corticotropin-releasing factor (CRF) system components, key effectors of the neuroendocrine stress response. Tolerance to HEA decreased markedly during embryonic development and early life HEA exposure increased ammonia tolerance in later life. While early life HEA has little impact on the cortisol stress response to a repeat HEA exposure, it abolished a later life stress response to a novel vortex stressor. In addition to their key role in stress signaling, CRF-related peptides are cytoprotective in certain tissues of other species. To test if this function is present in zebrafish during development, I examined the neurotoxic effects of HEA on constituents of the CNS in developing zebrafish and used ammonia neurotoxicity to evaluate the cytoprotective effects of CRF. Pre-treatment with CRF reversed the inhibitory effects of HEA exposure on the expression of the neuronal marker NeuroD in vivo, and prevented HEA-induced cell death in intact ex vivo larval brains. Finally, I provided novel evidence for the expression of all members of the CRF system in the zebrafish heart, that cardiac CRF and urocortin 3 gene expression are hypoxia-responsive, and that both peptides are cardioprotective against a hypoxic challenge. Together these findings expand our understanding of the early life effects of stressors on the neuroendocrine stress response and implies that HEA exposure can lead to sustained deficits in stress sensing in later life. Moreover, the protective effects of CRF-related peptides against HEA and hypoxia illustrate that cytoprotection is a strongly conserved feature of the CRF system among vertebrates and point to a broader role for the CRF system in the physiological homeostatic mechanisms against environmental stressors in fish.
URI: http://hdl.handle.net/10214/11936
Date: 2017-11-06


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