3,3'-Dichlorobiphenyl (PCB 11) promotes dendritic arborization in primary rat cortical neurons via a CREB-dependent mechanism

Archives of Toxicology
Sunjay SethiPamela J Lein

Abstract

PCB 11 (3,3'-dichlorobiphenyl), a contemporary congener produced as a byproduct of current pigment production processes, has recently emerged as a prevalent worldwide pollutant. We recently demonstrated that exposure to PCB 11 increases dendritic arborization in vitro, but the mechanism(s) mediating this effect remain unknown. To address this data gap, primary cortical neuron-glia co-cultures derived from neonatal Sprague-Dawley rats were exposed for 48 h to either vehicle (0.1% DMSO) or PCB 11 at concentrations ranging from 1 fM to 1 nM in the absence or presence of pharmacologic antagonists of established molecular targets of higher chlorinated PCBs. Reporter cell lines were used to test activity of PCB 11 at the aryl hydrocarbon receptor (AhR) and thyroid hormone receptor (THR). PCB 11 lacked activity at the AhR and THR, and antagonism of these receptors had no effect on the dendrite-promoting activity of PCB 11. Pharmacologic antagonism of various calcium channels or treatment with antioxidants also did not alter PCB 11-induced dendritic arborization. In contrast, pharmacologic blockade or shRNA knockdown of cAMP response element-binding protein (CREB) significantly decreased dendritic growth in PCB 11-exposed cultures, sug...Continue Reading

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Citations

Nov 13, 2019·Environmental Science and Pollution Research International·Carolyn KlockePamela J Lein
Feb 9, 2020·International Journal of Molecular Sciences·Carolyn Klocke, Pamela J Lein
Jun 13, 2020·Critical Reviews in Toxicology·Deepika DeepikaVikas Kumar
Sep 23, 2020·Toxics·Harmanpreet Kaur PanesarPamela J Lein
Jun 11, 2021·Chemical Research in Toxicology·Rumasha N T Kankanamage, Jana Sefcikova

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Methods Mentioned

BETA
chemical treatment
dissections
transfection

Software Mentioned

GraphPad Prism
ImageExpressXL
Metaxpress

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