Zebrafish embryos and Larvae : a new generation of disease model and drug screens

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Zebrafish embryos and Larvae : a new generation of disease model and drug screens

Title: Zebrafish embryos and Larvae : a new generation of disease model and drug screens
Author: Ali, Shaukat
Publisher: Research Group Integrative Zoology, Institute of Biology (IBL), Faculty of Science, Leiden University
Issue Date: 2011-12-07
Keywords: Behavior
Biochip
Drug discovery
Drug screens
Ethanol
Fetal alcohol syndrome
Microfuidics
Predictive model
Safety pharmacology
Toxicity
Zebrafish embryos
Abstract: Technological innovation has helped the zebrafish embryo gain ground as a disease model and an assay system for drug screening. Here, we review the use of zebrafish embryos and early larvae in applied biomedical research, using selected cases. We look at the use of zebrafish embryos as disease models, taking fetal alcohol syndrome and tuberculosis as examples. We discuss advances in imaging, in culture techniques (including microfluidics), and in drug delivery (including new techniques for the robotic injection of compounds into the egg). The use of zebrafish embryos in early stages of drug safety-screening is discussed. So too are the new behavioral assays that are being adapted from rodent research for use in zebrafish embryos, and which may become relevant in validating the effects of neuroactive compounds such as anxiolytics and antidepressants. Readouts, such as morphological screening and cardiac function, are examined. There are several drawbacks in the zebrafish model. One is its very rapid development, which means that screening with zebrafish is analogous to “screening on a run-away train.” Therefore, we argue that zebrafish embryos need to be precisely staged when used in acute assays, so as to ensure a consistent window of developmental exposure. We believe that zebrafish embryo screens can be used in the pre-regulatory phases of drug development, although more validation studies are needed to overcome industry scepticism. Finally, the zebrafish poses no challenge to the position of rodent models: it is complementary to them, especially in early stages of drug research.
Description: Promotor: Michael K. Richardson
With summary in Dutch
Supervisor:
Faculty: Faculteit der Wiskunde en Natuurwetenschappen
Citation: Ali, S., 2011, Doctoral thesis, Leiden University
ISBN: 9789085707318
Sponsor: This work described in this thesis was supported by the Smart Mix Programme of the Netherlands Ministry of Economic Affairs and the Netherlands Ministry of Education, Culture and Science under grant number" SSM06010" and University of Azad Jammu and Kashmir, Pakistan under project "No.F-3/PD/Main & Mirpur/369/2007.
Handle: http://hdl.handle.net/1887/18191
 

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application/pdf Chapter 1 General introduction and discussion 750.8Kb View/Open Full text at publisher site
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