Vijayan, MathilakathShvartsburd, Zachary Skyler2024-08-202024-08-202024-08-16Shvartsburd, Z. S. (2024). The role of corticotropin-releasing hormone receptor 1 in the heat shock-mediated behavioural and metabolic response in zebrafish (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.https://hdl.handle.net/1880/119445Activation of the primary stress response, the hypothalamic-pituitary-adrenal (HPA)-axis in mammals or the hypothalamic-pituitary-interrenal (HPI)-axis in fish, requires the binding of corticotropin-releasing hormone (CRH) to CRH receptor 1 (CRHR1), though CRHR1 activity is also implicated in behavioural adjustment and peripheral signalling not associated with the HPI-axis. With global water temperatures rising and daily temperature fluctuations becoming more extreme, the stress response may be a critical mechanism of aquatic species to withstand shifts in temperature. By using a ubiquitous CRHR1 knockout (CRHR1KO) model, I investigated the hypothesis that CRHR1 is involved in the behavioural and metabolic modulation of the developmental and adult life stage stress response during acute heat shock in zebrafish. Following a 1-hour +5°C heat shock, wildtype (WT) fish larvae showed an increase in swimming activity but CRHR1KO larvae failed to respond to the heat shock. Basal oxygen consumption between WT and CRHR1KO larvae were similar, but CRHR1KO had elevated oxygen consumption in non-mitochondrial and ATP-linked processes. Cardiac performance was unchanged between WT and CRHR1KO larvae, indicating differences in behaviour were not due to modulation of heart function. Adult WT zebrafish showed the same increase in swimming activity when exposed to acute heat shock, while CRHR1KO fish had no change in swimming behaviour. The metabolic rate (MO2) of WT adult fish also increased with heat shock, but this was not associated with increased circulating cortisol, as exposure to metyrapone, an inhibitor of cortisol synthesis, failed to attenuate the heat shock-induced rise in MO2. The MO2 of CRHR1KO fish did not increase following heat shock, suggesting CRHR1 action independent of the HPI-axis. Swimming performance was impaired in the CRHR1KO, with a lower aerobic scope and Ucrit compared to WT. Transcript and metabolite analysis in the muscle revealed potential futile cycling of glycogen in CRHR1KO fish. In summary, my study shows CRHR1 as a key integrator of the behavioural and metabolic rate response which improves performance following an acute heat shock, implicating CRHR1 as a metabolic thermal sensor for ectotherms.enUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.stress physiologyzebrafishheat shockHPI-axisCRHR1behaviourmetabolic rateAnimal Physiologymaster thesis