PUBLICATION
Coordinated action of CRH and cortisol shapes acute stress-induced behavioural response in zebrafish
- Authors
- Faught, E., Vijayan, M.M.
- ID
- ZDB-PUB-210128-29
- Date
- 2021
- Source
- Neuroendocrinology 112(1): 74-87 (Journal)
- Registered Authors
- Faught, Erin, Vijayan, Mathilakath
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Behavior, Animal/physiology*
- Corticotropin-Releasing Hormone/metabolism*
- Hydrocortisone/metabolism*
- Hypothalamo-Hypophyseal System/metabolism*
- Larva
- Locomotion/physiology*
- Receptors, Corticotropin-Releasing Hormone/genetics
- Receptors, Corticotropin-Releasing Hormone/metabolism*
- Stress, Psychological/metabolism*
- Stress, Psychological/physiopathology*
- Zebrafish
- Zebrafish Proteins
- PubMed
- 33503614 Full text @ Neuroendocrinology
Citation
Faught, E., Vijayan, M.M. (2021) Coordinated action of CRH and cortisol shapes acute stress-induced behavioural response in zebrafish. Neuroendocrinology. 112(1):74-87.
Abstract
Introduction The stress response mediated by the hypothalamus-pituitary-adrenal (HPA) axis activation is highly conserved in vertebrates. Hyperactivity is one such established acute stress response and corticotropin-releasing hormone (CRH), the primary step in HPA activation, signalling has been implicated in this stressor-mediated behaviour. However, whether CRH mediates the acute behavioural effects either alone or in conjunction with glucocorticoids (GCs) are far from clear. We hypothesized that the CRH receptor 1 (CRHR1)-mediated rise in GCs post-stress is necessary for the initiation and maintenance of acute stress-related behaviour.
Methods We first generated zebrafish (Danio rerio) with a mutation in the crhr1 gene (CRHR1-KO) to assess the function of CRH. The behavioural readout utilized for this study was the locomotor activity of larval zebrafish in response to acute light exposure, a protocol that freezes the larvae in response to the light stimulus. To test whether cortisol signalling is involved in the stress-mediated hyperactivity, we treated wildtype fish with metyrapone, an inhibitor of 11β-hydroxylase, to suppress cortisol production. The temporal role for cortisol signalling in the stress-related hyperactivity was tested using the glucocorticoid receptor (GRKO) and mineralocorticoid receptor (MRKO) knockout zebrafish mutants.
Results CRHR1-KO larvae did not increase cortisol, the principal GC in teleosts, post-stress, confirming a functional knockout. An acute stress resulted in the hyperactivity of the larvae in light at 15, 60 and 240 min post-stress and this was absent in CRHR1-KO larvae. Addition of metyrapone effectively blocked the attendant rise in cortisol post-stress; however, the stress-mediated hyperactivity was inhibited only at 60 min and 240 min but not at 15 min post-stress. Addition of human CRH peptide caused hyperactivity at 15 min and this response was also abolished in the CRHR1-KO mutants. The stress-induced hyperactivity was absent in the MRKO fish, while GRKO mutants showed transient effects.
Conclusions The results suggest that the stress-induced hyperactivity is induced by the CRH/CRHR1 system, while the temporal activation of cortisol production and the associated GR/MR signalling is essential for prolonging the stressor-induced hyperactivity. This study underscores the importance of systems-level analysis to assess stress responsivity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping