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

Neurotoxicol Teratol. 2022 Sep-Oct:93:107121. doi: 10.1016/j.ntt.2022.107121. Epub 2022 Sep 9.

Abstract

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.

Keywords: Aging; Benzo-a-pyrene; Neurobehavioral toxicology; Polycyclic hydrocarbon; Zebrafish.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzo(a)pyrene / toxicity
  • Creosote / metabolism
  • Creosote / pharmacology
  • Environmental Pollutants*
  • Larva
  • Petroleum* / metabolism
  • Polycyclic Aromatic Hydrocarbons*
  • Tobacco Smoke Pollution*
  • Zebrafish

Substances

  • Environmental Pollutants
  • Petroleum
  • Polycyclic Aromatic Hydrocarbons
  • Tobacco Smoke Pollution
  • Benzo(a)pyrene
  • Creosote