TitleDevelopmental and behavioral alterations in zebrafish embryonically exposed to valproic acid (VPA): An aquatic model for autism.
Publication TypeJournal Article
Year of Publication2018
AuthorsChen, J, Lei, L, Tian, L, Hou, F, Roper, C, Ge, X, Zhao, Y, Chen, Y, Dong, Q, Tanguay, RL, Huang, C
JournalNeurotoxicol Teratol
Volume66
Pagination8-16
Date Published2018 Mar - Apr
ISSN1872-9738
Abstract

Autism spectrum disorder (ASD) has complex neurodevelopmental impairments and origins that are linked to both genetic and environmental factors. Hence, there is an urgency to establish animal models with ASD-like characteristics to understand the underlying mechanisms of ASD. Prenatal exposure to valproic acid (VPA) produced ASD-like symptoms in humans, rats, and recently zebrafish. The present study investigated the use of VPA exposure to generate an ASD model in zebrafish. Early life stage exposures produced ASD-like phenotypes in the developing brain development and behavioral changes in embryonic and larval zebrafish. Our findings revealed that treating zebrafish embryos with VPA starting at 8h post fertilization (hpf) resulted in significant: increase in the ASD macrocephalic phenotype; hyperactivity of embryo/larvae movement behaviors; and increases of ASD-like larval social behaviors. Further analysis showed increases in cell proliferation, the proportion of mature newborn neurons, and neural stem cell proliferation in the brain region, which may contribute to the brain overgrowth and macrocephaly observed following VPA exposure. Our study demonstrated that VPA exposure generates ASD-like phenotypes and behaviors, indicating that zebrafish is an alternative model to investigate underlying ASD mechanisms.

DOI10.1016/j.ntt.2018.01.002
Alternate JournalNeurotoxicol Teratol
PubMed ID29309833
PubMed Central IDPMC5856631
Grant ListT32 ES007060 / ES / NIEHS NIH HHS / United States