RP2E INRA Université de Lorraine

Toxicogenomic profiles in neurons of male mice following early low exposure to the six indicator non-dioxin-like polychlorinated biphenyls

“4th Global Summit on Toxicology”, 24-26 august, Philadelphie, Etats-Unis

Ardzivian, A., Desor, F., Marin, F., Soulimani, R., Nemos, C.


We have previously shown neurobiological changes and developmental/behavioral performances in mice exposed during lactation to a representative environmental mixture of the six indicator non-dioxin-like polychlorinated biphenyls (?6 NDL-PCBs) at low levels. In this study, we analyzed the global gene expression profile in cerebellar neurons isolated from male mice presenting the most significant induction of anxiety-like behavior in our previous study (10 ng/kg ?6 NDL-PCBs). Our results revealed an upregulation in the expression of genes belonging to GO terms involved with the cell cycle, DNA replication, cell cycle checkpoint, response to DNA damage stimulus, regulation of RNA biosynthetic processes, and microtubule cytoskeleton organization. Downregulated genes belonged to terms involved with the transmission of nerve impulses, projection neurons, synapse hands, cell junctions, and regulation of RNA biosynthetic processes. Using qPCR, we quantified gene expression related to DNA damage and validated the transcriptomic study, as a significant overexpression of Atm, Atr, Bard1, Brca2, Fancd2, Figf, Mycn, p53 and Rad51 was observed between groups. Finally, using immunoblots, we found significant changes in the protein expression of Atm, Brca1, p53, Kcnma1, Npy4r and Scn1a between exposed and control groups, indicating  that the expression pattern of these proteins agreed with the expression pattern of their genes by qPCR, further validating our transcriptomic findings. In conclusion, our study showed that early life exposure of male mice to a low level of ?6 NDL-PCBs induced p53-dependent responses to cellular stress and a decrease in the expression of proteins involved in the generation, conduction, and transmission of electrical signals in neurons.

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