Using zebrafish to assess the impact of drugs on neural development and function

Abstract

Background: Zebrafish is becoming an increasingly attractive model organism for understanding biology and developing therapeutics, because as a vertebrate, it shares considerable similarity with mammals in both genetic compositions and tissue/organ structures, and yet remains accessible to high throughput phenotype-based genetic and small molecule compound screening. Objective/method: The focus of this review is on the nervous system, which is arguably the most complex organ and known to be afflicted by > 600 disorders in humans. I discuss the past, present and future of using zebrafish to assess the impact of small molecule drugs on neural development and function, in light of understanding and treating neurodevelopmental disorders such as autism, neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's disease and neural system dysfunctions such as anxiety/depression and addiction. Conclusion: These studies hold promise to reveal fundamental mechanisms governing nervous system development and function, and to facilitate small molecule drug discovery for the many types of neurological disorders.

Keywords::

• addiction
• Alzheimer's disease
• anxiety/depression
• autism
• function
• Huntington's disease
• neural development
• neurodegeneration
• neurological disorders
• Parkinson's disease
• small molecule drug discovery
• zebrafish

Acknowledgments

I apologize to authors whose work cannot be cited in this review owing to space limitations. I thank S. Chatterjee, E. Hurlock, T. Mueller and Y. Sun for helpful comments on the review.