@article{60b7d21ecae845c2990c419285a20333,
title = "Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response",
abstract = "When vertebrates face acute stressors, their bodies rapidly undergo a repertoire of physiological and behavioral adaptations, which is termed the stress response. Rapid changes in heart rate and blood glucose levels occur via the interaction of glucocorticoids and their cognate receptors following hypothalamic-pituitary-adrenal axis activation. These physiological changes are observed within minutes of encountering a stressor and the rapid time domain rules out genomic responses that require gene expression changes. Although behavioral changes corresponding to physiological changes are commonly observed, it is not clearly understood to what extent hypothalamic-pituitary-adrenal axis activation dictates adaptive behavior. We hypothesized that rapid locomotor response to acute stressors in zebrafish requires hypothalamic-pituitary-interrenal (HPI) axis activation. In teleost fish, interrenal cells are functionally homologous to the adrenocortical layer. We derived eight frameshift mutants in genes involved in HPI axis function: two mutants in exon 2 of mc2r (adrenocorticotropic hormone receptor), five in exon 2 or 5 of nr3c1 (glucocorticoid receptor [GR]) and two in exon 2 of nr3c2 (mineralocorticoid receptor [MR]). Exposing larval zebrafish to mild environmental stressors, acute changes in salinity or light illumination, results in a rapid locomotor response. We show that this locomotor response requires a functioning HPI axis via the action of mc2r and the canonical GR encoded by nr3c1 gene, but not MR (nr3c2). Our rapid behavioral assay paradigm based on HPI axis biology can be used to screen for genetic and environmental modifiers of the hypothalamic-pituitary-adrenal axis and to investigate the effects of corticosteroids and their cognate receptor interactions on behavior.",
keywords = "HPA axis, assay development, behavioral genetics, cortisol, custom nuclease, glucocorticoid receptor",
author = "Lee, {Han B.} and Schwab, {Tanya L.} and Sigafoos, {Ashley N.} and Gauerke, {Jennifer L.} and Krug, {Randall G.} and Serres, {Ma Kayla R.} and Jacobs, {Dakota C.} and Cotter, {Ryan P.} and Biswadeep Das and Petersen, {Morgan O.} and Daby, {Camden L.} and Urban, {Rhianna M.} and Berry, {Bethany C.} and Clark, {Karl J.}",
note = "Funding Information: information National Institute of Diabetes and Digestive and Kidney Diseases, Grant/Award Number: DK84567; National Institute of General Medical Sciences, Grant/Award Number: GM63904; National Institute on Drug Abuse, Grant/Award Number: DA032194; Mayo ClinicWe thank for their advice on experiments: Thesis advisory committee (Stephen C. Ekker, PhD, John R. Henley, PhD, Joseph A. Murray, MD, Robin Patel, MD, Susannah J. Tye, PhD) for Han B. Lee, zebrafish model seminar group (Christopher K. Pierret, PhD, Lisa A. Schimmenti, MD, Caroline R. Sussman, PhD, Shizhen [Jane] Zhu, MD, PhD), and Neuroscience Program (Allan J. Bieber, PhD, DooSup Choi, PhD, John D. Fryer, PhD, Pamela J. McLean, PhD, Owen A. Ross, PhD, Isobel A. Scarisbrick, PhD). For zebrafish husbandry: Mayo Clinic Zebrafish Core Facility (Tammy M. Greenwood, MS, MBA, Danielle E. Hunter, Devin B. Copley, Casey M. Phillips), Mayo Clinic Gene Editing Core (Camden L. Daby, Melissa S. McNulty, MS). For engineering light boxes: Mayo Clinic Division of Engineering (Allen K. Rech, PMP, Shaun A. Herring, Roger J. Mahon, Daniel J. [Clay] Mangiameli). For literature search: Julie A. Swenson and other Mayo Clinic Library staff. For funding this project: National Institute of General Medical Sciences (GM63904), National Institute of Diabetes and Digestive and Kidney Diseases (DK84567), National Institute on Drug Abuse (DA032194) and Mayo Clinic Center for Cell Signaling in Gastroenterology Pilot and Feasibility Award. For reviewing the manuscript: Louis El Khoury, PhD, Noriko Ichino, PhD, and Jennifer M. Reiman, PhD. Publisher Copyright: {\textcopyright} 2018 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.",
year = "2019",
month = feb,
doi = "10.1111/gbb.12549",
language = "English (US)",
volume = "18",
journal = "Genes, Brain and Behavior",
issn = "1601-1848",
publisher = "Wiley-Blackwell",
number = "2",
}