Journal article
3,3'-Dichlorobiphenyl (PCB 11) promotes dendritic arborization in primary rat cortical neurons via a CREB-dependent mechanism
Archives of toxicology, Vol.92(11), pp.3337-3345
11/01/2018
DOI: 10.1007/s00204-018-2307-8
PMCID: PMC6196112
PMID: 30225637
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 48h to either vehicle (0.1% DMSO) or PCB 11at concentrations ranging from 1 fM to 1nM 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 11at 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, suggesting PCB 11 promotes dendritic growth via CREB-mediated mechanisms. Since CREB signaling is crucial for normal neurodevelopment, and perturbations of CREB signaling have been associated with neurodevelopmental disorders, our findings suggest that this contemporary pollutant poses a threat to the developing brain, particularly in individuals with heritable mutations that promote CREB signaling.
Details
- Title: Subtitle
- 3,3'-Dichlorobiphenyl (PCB 11) promotes dendritic arborization in primary rat cortical neurons via a CREB-dependent mechanism
- Creators
- Sunjay Sethi - University of California, DavisKimberly P. Keil - Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, 1089 Vet Med Dr, Davis, CA 95616 USAPamela J. Lein - University of California, Davis
- Resource Type
- Journal article
- Publication Details
- Archives of toxicology, Vol.92(11), pp.3337-3345
- DOI
- 10.1007/s00204-018-2307-8
- PMID
- 30225637
- PMCID
- PMC6196112
- NLM abbreviation
- Arch Toxicol
- ISSN
- 0340-5761
- eISSN
- 1432-0738
- Publisher
- Springer Nature
- Number of pages
- 9
- Grant note
- T32ES007059 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) U54 HD079125 / MIND Institute Intellectual and Developmental Disabilities Research Center U54HD079125 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) P42 ES013661 / Superfund Research Center at The University of Iowa R01 ES014901; P30 ES023513; P01 ES011269; T32 ES007059; F32 HD088016 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 11/01/2018
- Academic Unit
- Iowa Superfund Research Program
- Record Identifier
- 9984297955902771
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