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Neurotoxicol Teratol. 2018 Mar - Apr;66:8-16. doi: 10.1016/j.ntt.2018.01.002. Epub 2018 Jan 5.

Developmental and behavioral alterations in zebrafish embryonically exposed to valproic acid (VPA): An aquatic model for autism.

Author information

1
Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035, China.
2
Environmental and Molecular Toxicology, The Sinnhuber Aquatic Research Laboratory and the Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97333, USA.
3
Environmental and Molecular Toxicology, The Sinnhuber Aquatic Research Laboratory and the Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97333, USA. Electronic address: Robert.Tanguay@oregonstate.edu.
4
Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: cjhuang5711@163.com.

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.

KEYWORDS:

Behaviors; Head size; Neural cells expression; VPA; Zebrafish

PMID:
29309833
PMCID:
PMC5856631
DOI:
10.1016/j.ntt.2018.01.002
[Indexed for MEDLINE]
Free PMC Article

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