Early-Life Benzo[a]Pyrene Exposure Causes Neurodegenerative Syndromes in Adult Zebrafish (Danio rerio) and the Mechanism Involved.

There is increasing recognition of the importance of early-life environmental exposures in health disorders at later-life stages. The aim of this study was to evaluate whether early-life exposure to benzo[a]pyrene (BaP) could induce neurodegenerative syndromes at later-life stages in zebrafish. Embryos were exposed to BaP at doses of 0, 0.05, 0.5, 5, and 50 nM from early embryogenesis to 96 h post-fertilization (hpf), then transferred to clean water and maintained for 365 days. We found that BaP decreased locomotor and cognitive ability, neurotransmitter levels of dopamine, 3,4-dihydroxyphenylacetic acid and norepinephrine; and induced loss of dopaminergic neurons and resulted in neurodegeneration. Additionally, BaP increased amyloid β protein and cell apoptosis in the adult zebrafish brain. Further, DNA methyltransferase 1 (DNMT1) and DNMT3a were up-regulated in 96 hpf larvae and the adult brain. MeDIP-sequencing data of the 96 hpf larvae identified 235 differentially methylated genes in promoter, with the fold change > 1.5. Guanylate cyclase 2F (gucy2f) and dopamine receptor D4 related sequence (drd4-rs) were hypermethylation promoters, whereas zinc finger C4H2 domain (zc4h2) was a hypomethylation promoter in 96 hpf larvae and the adult brain. The mRNA levels of gucy2f and drd4-rs were down-regulated, and zc4h2 was up-regulated. Our findings suggested that the lasting modifications of DNA methylation were associated with neurodegenerative syndromes in adult zebrafish as a result of early-life BaP exposure. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Citation

Dongxu Gao, Chonggang Wang, Zhihui Xi, Yixi Zhou, Yuanchuan Wang, Zhenghong Zuo. Early-Life Benzo[a]Pyrene Exposure Causes Neurodegenerative Syndromes in Adult Zebrafish (Danio rerio) and the Mechanism Involved. Toxicological sciences : an official journal of the Society of Toxicology. 2017 May 01;157(1):74-84

PMID: 28329817

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