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Large Scale Zebrafish-Based In vivo Small Molecule Screen
Published on: December 30, 2010
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Identification of pathways that regulate circadian rhythms using a larval zebrafish small molecule screen
Eric A Mosser1,2, Cindy N Chiu1,3, T Katherine Tamai4
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Scientific Reports
|August 29, 2019
Summary
Researchers screened zebrafish to find new ways to regulate the body clock (circadian rhythms). They discovered that inflammation impacts circadian rhythms, offering new targets for treating sleep and other circadian rhythm disorders.
Area of Science:
- Chronobiology
- Zebrafish models
- Drug discovery
Background:
- The circadian clock regulates daily biological processes.
- Understanding circadian regulation in whole organisms is crucial.
- Previous studies primarily used cell cultures, potentially missing systemic effects.
Purpose of the Study:
- To identify novel molecular pathways influencing circadian rhythms in vivo.
- To investigate the role of systemic factors, like inflammation, in circadian regulation.
- To discover potential therapeutic targets for circadian rhythm disorders.
Main Methods:
- Conducted a small molecule screen using luminescent zebrafish larvae reporting molecular circadian rhythms.
- Tested identified compounds on cultured zebrafish and mammalian cell lines.
- Investigated the effect of anti-inflammatory drugs and a microglia-deficient mutant on circadian rhythms.
Main Results:
- Identified known and novel pathways affecting circadian period, amplitude, and phase in intact zebrafish.
- Several compounds effective in vivo showed no effect in cell culture, indicating organism-specific mechanisms.
- Inflammatory state was found to significantly impact circadian amplitude, modulated by microglia.
Conclusions:
- Screening in intact animals is essential for discovering systemic drug effects on circadian rhythms.
- Inflammation represents a novel modulator of circadian clock function.
- Findings provide new therapeutic targets for circadian rhythm disorders.
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