Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response.

Autor: Lee HB; Neuroscience Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, Minnesota., Schwab TL; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota., Sigafoos AN; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota., Gauerke JL; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota., Krug RG 2nd; Neuroscience Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, Minnesota., Serres MR; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota., Jacobs DC; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota., Cotter RP; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota., Das B; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota., Petersen MO; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota., Daby CL; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota., Urban RM; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota., Berry BC; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota., Clark KJ; Neuroscience Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, Minnesota.; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota.
Jazyk: angličtina
Zdroj: Genes, brain, and behavior [Genes Brain Behav] 2019 Feb; Vol. 18 (2), pp. e12549. Date of Electronic Publication: 2019 Jan 15.
DOI: 10.1111/gbb.12549
Abstrakt: 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.
(© 2018 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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