Identification of pathways that regulate circadian rhythms using a larval zebrafish small molecule screen
| Autor: | Tsuyoshi Hirota, May Hui, David A. Prober, Suna Li, Eric A. Mosser, Steve A. Kay, Chanpreet Singh, Amy Wang, Andrew Giovanni, Cindy N. Chiu, T. Katherine Tamai |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Taurine Period (gene) Circadian clock Mutant lcsh:Medicine Article Animals Genetically Modified Small Molecule Libraries 03 medical and health sciences 0302 clinical medicine Receptors Glycine medicine Animals Circadian rhythm lcsh:Science Receptor Zebrafish Protein Kinase Inhibitors Multidisciplinary Microglia biology Casein Kinase I lcsh:R Anti-Inflammatory Agents Non-Steroidal Zebrafish Proteins biology.organism_classification Small molecule 3. Good health Cell biology Circadian Rhythm 030104 developmental biology medicine.anatomical_structure Larva Circadian regulation Screening lcsh:Q 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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