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Volume 6, Issue 6(Suppl)
J Clin Toxicol 2016
ISSN: 2161-0495, JCT an open access journal
Page 77
Notes:
Euro Toxicology 2016
October 24-26, 2016
conferenceseries
.com
Toxicology & Applied Pharmacology
October 24-26, 2016 Rome, Italy
7
th
Euro-Global Summit on
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
Walter Lichtensteiger
1
, Catherine Bassetti-Gaille
1
, Hubert Rehrauer
2,3,4
, Jelena Kühn Georgijevic
2,3,4
, Margret Schlumpf
1
and
Jesus A F Tresguerres
5
1
GREEN Tox, Switzerland
2
Institute of Veterinary Pharmacology and Toxicology, Switzerland
3
University of Zurich, Switzerland
4
Swiss Federal Institute of Technology, Switzerland
5
Universidad Complutense, Madrid
D
evelopmental 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 post-
transcriptional 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.
walter.lichtensteiger@access.uzh.chWalter Lichtensteiger et al., J Clin Toxicol 2016, 6:6(Suppl)
http://dx.doi.org/10.4172/2161-0495.C1.021