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A zebrafish model for calcineurin-dependent brain function
Sara Tucker Edmister1, Rahma Ibrahim1, Rohit Kakodkar2
1Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA.
Behavioural Brain Research
|August 23, 2021
Summary
Small molecules targeting calcineurin signaling impact zebrafish behavior. Calcineurin inhibitors caused hyperactivity, while proINDY reduced activity, suggesting pathway regulation of neural function.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- Calcineurin signaling is implicated in Down syndrome and Alzheimer's disease.
- Small molecules like proINDY, cyclosporine, and tacrolimus modulate calcineurin activity.
- Understanding their behavioral effects is crucial for therapeutic development.
Purpose of the Study:
- To investigate the behavioral effects of proINDY, cyclosporine, and tacrolimus in zebrafish larvae.
- To assess the role of calcineurin-NFAT signaling in regulating behavior.
- To evaluate a high-throughput platform for testing modulators of calcineurin signaling.
Main Methods:
- Zebrafish larvae were treated with calcineurin inhibitors (cyclosporine, tacrolimus) or activator (proINDY).
- Behavioral assays included activity levels, visually-guided behaviors, and acoustic responses.
- Co-treatments were used to examine synergistic or opposing effects.
Main Results:
- Calcineurin inhibitors induced hyperactivity and impaired visually-guided and acoustic behaviors.
- ProINDY reduced activity and enhanced visually-guided behaviors, opposing inhibitor effects.
- Combined treatments showed therapeutic potential for some behaviors but increased excitability.
Conclusions:
- Calcineurin-NFAT signaling plays a key role in regulating zebrafish activity and visually-guided behaviors.
- Modulators can have opposing effects, highlighting pathway complexity.
- The study presents a platform for evaluating neural function restoration and side effects.
