PUBLICATION
Early-Life Benzo[a]Pyrene Exposure Causes Neurodegenerative Syndromes in Adult Zebrafish (Danio rerio) and the Mechanism Involved
- Authors
- Gao, D., Wang, C., Xi, Z., Zhou, Y., Wang, Y., Zuo, Z.
- ID
- ZDB-PUB-170323-2
- Date
- 2017
- Source
- Toxicological sciences : an official journal of the Society of Toxicology 157(1): 74-84 (Journal)
- Registered Authors
- Keywords
- DNA methylation., benzo[a]pyrene, early-life stages, neurodegenerative disease, zebrafish
- MeSH Terms
-
- Amyloid beta-Peptides/metabolism
- Animals
- Apoptosis/drug effects
- Benzo(a)pyrene/toxicity*
- Brain/cytology
- Brain/drug effects
- DNA (Cytosine-5-)-Methyltransferase 1/metabolism
- DNA Methylation
- Dose-Response Relationship, Drug
- Environmental Exposure
- Female
- Locomotion/drug effects
- Neurodegenerative Diseases/chemically induced*
- Neurons/drug effects
- Neurons/metabolism
- Neurotransmitter Agents/metabolism
- Peptide Fragments/metabolism
- Pregnancy
- Prenatal Exposure Delayed Effects*
- RNA, Messenger/metabolism
- Zebrafish/embryology*
- PubMed
- 28329817 Full text @ Toxicol. Sci.
- CTD
- 28329817
Citation
Gao, D., Wang, C., Xi, Z., Zhou, Y., Wang, Y., Zuo, Z. (2017) 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. 157(1):74-84.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping