Walter Lichtensteiger
GREEN Tox, Switzerland
Title: 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
Biography
Biography: Walter Lichtensteiger
Abstract
Developmental exposure to polychlorinated biphenyls (PCBs), bisphenol A (BPA) or the pesticide chlorpyrifos (CPF) impairs hippocampus-dependent behaviors (learning) in adult off spring. In a search for shared eff ects 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 off spring at postnatal day six (PND6) by NGS. In male hippocampus, analyses revealed common eff ects 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 aff ected by only two treatments. Eff ects on Sox6, Nrg1, Erbb4, Oct1 were confi rmed by real time RT PCR. Analyses of proteins and female hippocampus are in progress. Involvement of Nrg1, its receptor Erbb4 and Sox6 suggests eff ects 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 specifi c eff ect in interneurons. Sox6 further controls gliogenesis in hippocampus; Sox6 overexpression represses specification and terminal diff erentiation of oligodendrocyte precursors. In conclusion, our investigation revealed convergent actions of diff erent types of behaviorally active chemicals on genes involved in the control of major developmental processes
in hippocampus.
