Identification of pathways that regulate circadian rhythms using a larval zebrafish small molecule screen.
Animals
Animals, Genetically Modified
/ physiology
Anti-Inflammatory Agents, Non-Steroidal
/ pharmacology
Casein Kinase I
/ antagonists & inhibitors
Circadian Rhythm
/ drug effects
Larva
/ drug effects
Protein Kinase Inhibitors
/ pharmacology
Receptors, Glycine
/ agonists
Small Molecule Libraries
/ pharmacology
Taurine
/ pharmacology
Zebrafish
/ growth & development
Zebrafish Proteins
/ antagonists & inhibitors
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 08 2019
27 08 2019
Historique:
received:
21
03
2018
accepted:
31
07
2019
entrez:
29
8
2019
pubmed:
29
8
2019
medline:
30
10
2020
Statut:
epublish
Résumé
The circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we performed a small molecule screen using a luminescent reporter of molecular circadian rhythms in zebrafish larvae. We identified both known and novel pathways that affect circadian period, amplitude and phase. Several drugs identified in the screen did not affect circadian rhythms in cultured cells derived from luminescent reporter embryos or in established zebrafish and mammalian cell lines, suggesting they act via mechanisms absent in cell culture. Strikingly, using drugs that promote or inhibit inflammation, as well as a mutant that lacks microglia, we found that inflammatory state affects circadian amplitude. These results demonstrate a benefit of performing drug screens using intact animals and provide novel targets for treating circadian rhythm disorders.
Identifiants
pubmed: 31455847
doi: 10.1038/s41598-019-48914-7
pii: 10.1038/s41598-019-48914-7
pmc: PMC6712016
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Protein Kinase Inhibitors
0
Receptors, Glycine
0
Small Molecule Libraries
0
Zebrafish Proteins
0
Taurine
1EQV5MLY3D
Casein Kinase I
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12405Subventions
Organisme : NINDS NIH HHS
ID : R01 NS095824
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS101665
Pays : United States
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