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

Neurotoxicol Teratol

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:

Published: January 2020

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856631PMC
http://dx.doi.org/10.1016/j.ntt.2018.01.002DOI Listing

Publication Analysis

Top Keywords

vpa exposure
12
valproic acid
8
acid vpa
8
produced asd-like
8
asd-like phenotypes
8
cell proliferation
8
zebrafish
6
vpa
6
asd
5
asd-like
5

Similar Publications

Exposure to valproic acid (VPA) during embryogenesis has become a valuable tool for modeling neurodevelopmental disorders in animal models such as zebrafish (). This article examines the effects of embryonic exposure to VPA in zebrafish on the basis of 39 articles sourced from PubMed and Google Scholar. We conducted a systematic review and meta-analysis to elucidate the common impacts of VPA exposure and reported that VPA significantly altered development at various levels.

View Article and Find Full Text PDF

Background: Recent guidance from UK health authorities strongly cautions against the use of valproic acid (VPA) in persons under 55 because of reevaluated risk of teratogenicity.

Objective: To summarize the extant literature documenting VPA-associated anatomical, behavioral, and cognitive teratogenicity.

Method: Pubmed, Medline, Cochrane Library, PsychInfo, Embase, Scopus, Web of Science, and Google Scholar were searched in accordance with PRISMA guidelines.

View Article and Find Full Text PDF

Unlabelled: Valproic acid (VPA) demonstrates teratogenic effects during pregnancy. Prenatal exposure to VPA may result in autism spectrum disorder (ASD) -like phenotypes. Apigenin, a natural flavonoid, has been shown to have neuroprotective impacts due to its antioxidant properties.

View Article and Find Full Text PDF

Prenatal exposure to valproic acid induces sex-specific alterations in rat cortical and hippocampal neuronal structure and function in vitro.

Prog Neuropsychopharmacol Biol Psychiatry

December 2024

Department of Biomedical Sciences, University of Guelph, 50 Stone Rd. E., Guelph, Ontario N1G 2W1, Canada. Electronic address:

There are substantial differences in the characteristics of males and females with an autism spectrum disorder (ASD), yet there is little knowledge surrounding the mechanistic underpinnings of these differences. The valproic acid (VPA) rodent model is based upon the human fetal valproate spectrum disorder, which is associated with increased risk of developing ASD. This model, which displays significant social, learning, and memory alterations, has therefore been widely used to further our understanding of specific biological features of ASD.

View Article and Find Full Text PDF

Introduction: In 2015, the FDA released a Drug Safety Communication regarding a possible link between opioid exposure during early pregnancy and an increased risk of fetal neural tube defects (NTDs). At the time, the indications for opioid use during pregnancy were not changed due to incomplete maternal toxicity data and limitations in human and animal studies. To assess these knowledge gaps, largescale animal studies are ongoing; however, state-of-the-art technologies have emerged as promising tools to assess otherwise non-standard endpoints.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!