Early life exposure to low levels of AHR agonist PCB126 (3,3’,4,4’,5- pentachlorobiphenyl) reprograms gene expression in adult brain
Karchner, Sibel I.
MetadataShow full item record
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.
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.
Suggested CitationPreprint: 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/1912/9298
Showing items related by title, author, creator and subject.
Tide-related changes in mRNA abundance of aromatases and estrogen receptors in the ovary and brain of the threespot wrasse Halichoeres trimaculatus Oh, Dae-Ju; Hur, Sung-Pyo; Bouchekioua, Selma; Takeuchi, Yuki; Udagawa, Shingo; Aluru, Neelakanteswar; Park, Yong-Ju; Park, Ji-Gweon; Kim, Se-Jae; Moon, Thomas W.; Vijayan, Mathilakath M.; Takemura, Akihiro (2018-05)The threespot wrasse (Halichoeres trimaculatus; Family Labridae) is a common coral reef species of the Indo-Pacific Ocean. Given that this species spawns daily at high tide (HT), we hypothesized that endocrine changes ...
Expansion of voltage-dependent Na+ channel gene family in early tetrapods coincided with the emergence of terrestriality and increased brain complexity Zakon, Harold H.; Jost, Manda C.; Lu, Ying (2010-11-29)Mammals have 10 voltage-dependent sodium (Nav) channel genes. Nav channels are expressed in different cell types with different sub-cellular distributions and are critical for many aspects of neuronal processing. The ...
Shanklin, D. Radford; Shokouh-Amiri, M. (2011-04-27)Dizygotic twins at 38 weeks with separate placentas: twin A, a 2479 gram female, was healthy after vaginal delivery. Five minutes later when the amnion of twin B was ruptured artificially, the cord prolapsed and could not ...