| RRC ID |
60028
|
| 著者 |
Mosser EA, Chiu CN, Tamai TK, Hirota T, Li S, Hui M, Wang A, Singh C, Giovanni A, Kay SA, Prober DA.
|
| タイトル |
Identification of pathways that regulate circadian rhythms using a larval zebrafish small molecule screen.
|
| ジャーナル |
Sci Rep
|
| Abstract |
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.
|
| 巻・号 |
9(1)
|
| ページ |
12405
|
| 公開日 |
2019-8-27
|
| DOI |
10.1038/s41598-019-48914-7
|
| PII |
10.1038/s41598-019-48914-7
|
| PMID |
31455847
|
| PMC |
PMC6712016
|
| MeSH |
Animals
Animals, Genetically Modified / physiology
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Casein Kinase I / antagonists & inhibitors
Casein Kinase I / metabolism
Circadian Rhythm / drug effects*
Larva / drug effects
Larva / physiology
Protein Kinase Inhibitors / pharmacology
Receptors, Glycine / agonists
Receptors, Glycine / metabolism
Small Molecule Libraries / pharmacology*
Taurine / pharmacology
Zebrafish / growth & development
Zebrafish / physiology*
Zebrafish Proteins / antagonists & inhibitors
Zebrafish Proteins / metabolism
|
| IF |
4.011
|
| 引用数 |
4
|
| リソース情報 |
| ゼブラフィッシュ |
s357 |
