Zebrafish as a systems toxicology model for developmental neurotoxicity testing

• Published in: Congenital anomalies Vol. 55; no. 1; pp. 1 - 16
• Main Authors: Nishimura, Yuhei, Murakami, Soichiro, Ashikawa, Yoshifumi, Sasagawa, Shota, Umemoto, Noriko, Shimada, Yasuhito, Tanaka, Toshio
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.02.2015; Wiley Subscription Services, Inc
• Subjects: ADME; Animals; Autism; Central Nervous System - drug effects; Central Nervous System - embryology; Central Nervous System - growth & development; developmental neurotoxicity; Drug Evaluation, Preclinical; Gene expression; Gene Expression Profiling; Humans; Neurogenesis - drug effects; Neurotoxicity; Neurotoxicity Syndromes - prevention & control; systems toxicology; Toxicology; Zebrafish; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; systems toxicology; zebrafish; ADME; developmental neurotoxicity; autism
• ISSN: 0914-3505; 1741-4520; 1741-4520
• DOI: 10.1111/cga.12079

The developing brain is extremely sensitive to many chemicals. Exposure to neurotoxicants during development has been implicated in various neuropsychiatric and neurological disorders, including autism spectrum disorder, attention deficit hyperactive disorder, schizophrenia, Parkinson's disease, and Alzheimer's disease. Although rodents have been widely used for developmental neurotoxicity testing, experiments using large numbers of rodents are time‐consuming, expensive, and raise ethical concerns. Using alternative non‐mammalian animal models may relieve some of these pressures by allowing testing of large numbers of subjects while reducing expenses and minimizing the use of mammalian subjects. In this review, we discuss some of the advantages of using zebrafish in developmental neurotoxicity testing, focusing on central nervous system development, neurobehavior, toxicokinetics, and toxicodynamics in this species. We also describe some important examples of developmental neurotoxicity testing using zebrafish combined with gene expression profiling, neuroimaging, or neurobehavioral assessment. Zebrafish may be a systems toxicology model that has the potential to reveal the pathways of developmental neurotoxicity and to provide a sound basis for human risk assessments.