Developmental exposure of zebrafish to vitamin D receptor acting drugs and environmental toxicants disrupts behavioral function.

Oliveri, Anthony N

Glazer, Lilah

Mahapatra, Debabrata

Kullman, Seth W

Levin, Edward D

2023-12-06T16:27:37Z

2023-12-06T16:27:37Z

2020-09

2023-12-06T16:27:37Z

Vitamin D receptor (VDR) signaling is important for optimal neurobehavioral development. Disruption of VDR signaling by environmental toxicants during early development might contribute to the etiology of behavioral dysfunction. In the current set of studies, we examined ten compounds known to affect VDR function in vitro for neurobehavioral effects in vivo in zebrafish. Zebrafish embryos were exposed to concentrations of the compounds in their water during the first 5 days post-fertilization. On day 5, the embryos were tested in an alternating light-dark locomotor assay using a computerized video tracking system. We found that most of the compounds produced significant changes in locomotor behavior in exposed zebrafish larvae, although the direction of the effect (i.e., hypo- or hyperactivity) and the sensitivity of the effect to changes in illumination condition varied across the compounds. The nature of the behavioral effects generally corresponded to the effects these compounds have been shown to exert on VDR. These studies lay a foundation for further investigation to determine whether behavioral dysfunction persists into adulthood and if so which behavioral functions are affected. Zebrafish can be useful for screening compounds identified in high throughput in vitro assays to provide an initial test for how those compounds would affect construction and behavioral function of a complex nervous system, helping to bridge the gap between in vitro neurotoxicity assays and mammalian models for risk assessment in humans.

S0892-0362(20)30053-2

0892-0362

1872-9738

https://hdl.handle.net/10161/29500

eng

Elsevier BV

Neurotoxicology and teratology

10.1016/j.ntt.2020.106902

Animals

Zebrafish

Neurotoxicity Syndromes

Receptors, Calcitriol

Pharmaceutical Preparations

Hazardous Substances

Behavior, Animal

Motor Activity

Habituation, Psychophysiologic

Reflex, Startle

Developmental exposure of zebrafish to vitamin D receptor acting drugs and environmental toxicants disrupts behavioral function.

Journal article

Levin, Edward D|0000-0001-7292-8084|0000-0002-5060-9602

106902

Duke

Nicholas School of the Environment

School of Medicine

Trinity College of Arts & Sciences

Basic Science Departments

Clinical Science Departments

Institutes and Centers

Pharmacology & Cancer Biology

Psychiatry & Behavioral Sciences

Duke Cancer Institute

Psychology & Neuroscience

Environmental Sciences and Policy

Institutes and Provost's Academic Units

University Institutes and Centers

Duke Institute for Brain Sciences

Initiatives

Duke Science & Society

Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences

Published

81