Embryonic exposure to benzo[a]pyrene causes age-dependent behavioral alterations and long-term metabolic dysfunction in zebrafish.

Hawkey, Andrew B

Piatos, Perry

Holloway, Zade

Boyda, Jonna

Koburov, Reese

Fleming, Elizabeth

Di Giulio, Richard T

Levin, Edward D

2023-12-06T14:21:15Z

2023-12-06T14:21:15Z

2022-09

2023-12-06T14:21:15Z

Polycyclic aromatic hydrocarbons (PAH) are products of incomplete combustion which are ubiquitous pollutants and constituents of harmful mixtures such as tobacco smoke, petroleum and creosote. Animal studies have shown that these compounds exert developmental toxicity in multiple organ systems, including the nervous system. The relative persistence of or recovery from these effects across the lifespan remain poorly characterized. These studies tested for persistence of neurobehavioral effects in AB* zebrafish exposed 5-120 h post-fertilization to a typical PAH, benzo[a]pyrene (BAP). Study 1 evaluated the neurobehavioral effects of a wide concentration range of BAP (0.02-10 μM) exposures from 5 to 120 hpf during larval (6 days) and adult (6 months) stages of development, while study 2 evaluated neurobehavioral effects of BAP (0.3-3 μM) from 5 to 120 hpf across four stages of development: larval (6 days), adolescence (2.5 months), adulthood (8 months) and late adulthood (14 months). Embryonic BAP exposure caused minimal effects on larval motility, but did cause neurobehavioral changes at later points in life. Embryonic BAP exposure led to nonmonotonic effects on adolescent activity (0.3 μM hyperactive, Study 2), which attenuated with age, as well as startle responses (0.2 μM enhanced, Study 1) at 6 months of age. Similar startle changes were also detected in Study 2 (1.0 μM), though it was observed that the phenotype shifted from reduced pretap activity to enhanced posttap activity from 8 to 14 months of age. Changes in the avoidance (0.02-10 μM, Study 1) and approach (reduced, 0.3 μM, Study 2) of aversive/social cues were also detected, with the latter attenuating from 8 to 14 months of age. Fish from study 2 were maintained into aging (18 months) and evaluated for overall and tissue-specific oxygen consumption to determine whether metabolic processes in the brain and other target organs show altered function in late life based on embryonic PAH toxicity. BAP reduced whole animal oxygen consumption, and overall reductions in total basal, mitochondrial basal, and mitochondrial maximum respiration in target organs, including the brain, liver and heart. The present data show that embryonic BAP exposure can lead to neurobehavioral impairment across the life-span, but that these long-term risks differentially emerge or attenuate as development progresses.

S0892-0362(22)00059-9

0892-0362

1872-9738

https://hdl.handle.net/10161/29476

eng

Elsevier BV

Neurotoxicology and teratology

10.1016/j.ntt.2022.107121

Animals

Zebrafish

Creosote

Benzo(a)pyrene

Environmental Pollutants

Petroleum

Tobacco Smoke Pollution

Larva

Polycyclic Aromatic Hydrocarbons

Embryonic exposure to benzo[a]pyrene causes age-dependent behavioral alterations and long-term metabolic dysfunction in zebrafish.

Journal article

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

107121

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

93