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Converging effects of a PCB mixture, bisphenol A and chlorpyrifos on the expression of genes regulating neural progenitor identity, interneuron development and gliogenesis in developing rat hippocampus
Journal of Clinical Toxicology

Journal of Clinical Toxicology
Open Access

ISSN: 2161-0495

+44 20 3868 9735

Converging effects of a PCB mixture, bisphenol A and chlorpyrifos on the expression of genes regulating neural progenitor identity, interneuron development and gliogenesis in developing rat hippocampus


7th Euro-Global Summit on Toxicology & Applied Pharmacology

October 24-26, 2016 Rome, Italy

Walter Lichtensteiger, Catherine Bassetti-Gaille, Hubert Rehrauer, Jelena K?¼hn Georgijevic, Margret Schlumpf and Jesus A F Tresguerres

GREEN Tox, Switzerland
Institute of Veterinary Pharmacology and Toxicology, Switzerland
University of Zurich, Switzerland
Swiss Federal Institute of Technology, Switzerland
Universidad Complutense, Madrid

Scientific Tracks Abstracts: J Clin Toxicol

Abstract :

Developmental exposure to polychlorinated biphenyls (PCBs), bisphenol A (BPA) or the pesticide chlorpyrifos (CPF) impairs hippocampus-dependent behaviors (learning) in adult offspring. In a search for shared effects on gene networks, we treated pregnant rats with PCB mixture Aroclor1254 (5, 0.5 mg/kg), BPA (5, 0.5 mg/kg), or CPF (3, 1 mg/kg) in the feed (PCB, BPA) or subcutaneously (CPF). Transcriptome analysis was done in hippocampus from offspring at postnatal day six (PND6) by NGS. In male hippocampus, analyses revealed common effects on genes regulating hippocampal development. At behaviorally active doses, all chemicals showed upregulation of Gli3, neuregulin1, Erbb4, Sox6, Sox11, Pou2f2/Oct2, Pou3f2/ Brn2 and Wnt receptors Fzd3 and Fzd6. microRNA-24 was down-regulated, indicating possible interactions with posttranscriptional regulation of Sox6. Pou2f1/Oct1, Pou3f3/Brn1, Sox2 and Sox17 was affected by only two treatments. Effects on Sox6, Nrg1, Erbb4, Oct1 were confirmed by real time RT PCR. Analyses of proteins and female hippocampus are in progress. Involvement of Nrg1, its receptor Erbb4 and Sox6 suggests effects on interneuron development. In postmitotic interneurons of PND6, Sox6 controlled interneuron subtype diversity. Expression changes were observed in interneuron-related genes. The increase of Sox6 mRNA levels relative to mRNA levels of Sox5, its counterpart in postmitotic corticofugal projection neurons also suggests a specific effect in interneurons. Sox6 further controls gliogenesis in hippocampus; Sox6 overexpression represses specification and terminal differentiation of oligodendrocyte precursors. In conclusion, our investigation revealed convergent actions of different types of behaviorally active chemicals on genes involved in the control of major developmental processes in hippocampus.

Biography :

Walter Lichtensteiger has served as a Professor of Pharmacology and Toxicology at the University of Zurich, Switzerland, with teaching obligations at the Swiss Federal Institute of Technology (ETH), Zurich and after retirement, he founded the spin-off company GREEN Tox (Group for Reproductive, Endocrine and Environmental Toxicology) in 2005, together with Margret Schlumpf. GREEN Tox focuses on “Research and continuous education on environmental chemicals”. He is a member of several committees of the OECD programme for testing of chemicals.

Email: [email protected]

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