title: Zebrafish as a systems toxicology model for developmental neurotoxicity testing.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Tsu, Japan; Mie University Medical Zebrafish Research Center, Tsu, Japan; Depertment of Systems Pharmacology, Mie University Graduate School of Medicine, Tsu, Japan; Department of Omics Medicine, Mie University Industrial Technology Innovation Institute, Tsu, Japan; Department of Bioinformatics, Mie University Life Science Research Center, Tsu, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Soichiro
authors.initials: S
authors.lastname: Murakami
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ashikawa
authors.forename: Shota
authors.initials: S
authors.lastname: Sasagawa
authors.forename: Noriko
authors.initials: N
authors.lastname: Umemoto
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Shimada
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D004353:Drug Evaluation, Preclinical; D020869:Gene Expression Profiling; D006801:Humans; D055495:Neurogenesis / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000517:prevention & control; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029961:Zebrafish Proteins
keywords: ADME; autism; developmental neurotoxicity; systems toxicology; zebrafish