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.
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
Dongxu
D
Gao
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.|State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, Fujian, China.
Chonggang
C
Wang
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
Zhihui
Z
Xi
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
Yixi
Y
Zhou
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
Yuanchuan
Y
Wang
State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.|State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, Fujian, China.
Zhenghong
Z
Zuo
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001921:Brain / Q000166:cytology / Q000187:drug effects; D000076123:DNA (Cytosine-5-)-Methyltransferase 1 / Q000378:metabolism; D019175:DNA Methylation; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D005260:Female; D008124:Locomotion / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*
D016229:Amyloid beta-Peptides; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; C075222:amyloid beta-protein (1-42); D001564:Benzo(a)pyrene; D000076123:DNA (Cytosine-5-)-Methyltransferase 1
benzo[a]pyrene; early-life stages; neurodegenerative disease; zebrafish; DNA methylation