Early life exposure to low levels of AHR agonist PCB126 (3,3’,4,4’,5- pentachlorobiphenyl) reprograms gene expression in adult brain

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2017-09Author
Aluru, Neelakanteswar
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Karchner, Sibel I.
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Glazer, Lilah
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https://hdl.handle.net/1912/9298As published
https://doi.org/10.1093/toxsci/kfx192Abstract
Early life exposure to environmental chemicals can have long-term consequences that are not always
apparent until later in life. We recently demonstrated that developmental exposure of zebrafish to low,
non-embryotoxic levels of 3,3’,4,4’,5-pentachlorobiphenyl (PCB126) did not affect larval behavior, but
caused changes in adult behavior. The objective of this study was to investigate the underlying
molecular basis for adult behavioral phenotypes resulting from early life exposure to PCB126. We
exposed zebrafish embryos to PCB126 during early development and measured transcriptional
profiles in whole embryos, larvae and adult male brains using RNA-sequencing. Early life exposure to
0.3 nM PCB126 induced cyp1a transcript levels in 2-dpf embryos, but not in 5-dpf larvae, suggesting
transient activation of aryl hydrocarbon receptor with this treatment. No significant induction of cyp1a
was observed in the brains of adults exposed as embryos to PCB126. However, a total of 2209 and
1628 genes were differentially expressed in 0.3 nM and 1.2 nM PCB126-exposed groups,
respectively. KEGG pathway analyses of upregulated genes in the brain suggest enrichment of
calcium signaling, MAPK and notch signaling, and lysine degradation pathways. Calcium is an
important signaling molecule in the brain and altered calcium homeostasis could affect neurobehavior.
The downregulated genes in the brain were enriched with oxidative phosphorylation and various
metabolic pathways, suggesting that the metabolic capacity of the brain is impaired. Overall, our
results suggest that PCB exposure during sensitive periods of early development alters normal
development of the brain by reprogramming gene expression patterns, which may result in alterations
in adult behavior.
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Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Toxicological Sciences 160 (2017): 386-397, doi:10.1093/toxsci/kfx192.
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Suggested Citation
Preprint: Aluru, Neelakanteswar, Karchner, Sibel I., Glazer, Lilah, "Early life exposure to low levels of AHR agonist PCB126 (3,3’,4,4’,5- pentachlorobiphenyl) reprograms gene expression in adult brain", 2017-09, https://doi.org/10.1093/toxsci/kfx192, https://hdl.handle.net/1912/9298Related items
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