Detection of 3,3'-Dichlorobiphenyl in human maternal plasma and its effects on axonal and dendritic growth in primary rat neurons

Sunjay Sethi, Kimberly P. Keil, Hao Chen, Keri Hayakawa, Xueshu Li, Yanping Lin, Hans Joachim Lehmler, Birgit Puschner, Pamela J Lein

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

3,3'-Dichlorobiphenyl (PCB 11), a byproduct of pigment production, is increasingly detected in environmental samples. While more highly chlorinated PCB congeners are known developmental neurotoxicants, nothing is known about the potential developmental neurotoxicity of PCB 11. To address this critical data gap, we measured PCB 11 levels in human maternal plasma and quantified the effects of PCB 11 and its major metabolites on morphometric parameters of neuronal connectivity in cultured primary neurons. Mass spectrometry analyses of plasma from 241 pregnant women enrolled in the MARBLES study (University of California, Davis) detected PCB 11 in all samples at concentrations ranging from 0.005 to 1.717 ng/ml. Morphometric analyses of primary neuron-glia co-cultures dissociated from the neocortices or hippocampi of neonatal Sprague Dawley rats exposed to vehicle or concentrations ranging from 1 attamolar (aM) to 1 micromolar (μM) of PCB 11, OH-PCB 11, or PCB 11 sulfate indicated that PCB 11 and both metabolites significantly increased axonal and dendritic growth in cortical and hippocampal pyramidal neurons. PCB 11 significantly altered neuronal morphogenesis at concentrations as low as 1 femtomolar (fM), which is ~0.22 ng/ml. These data suggest the potential for the developing human brain to be exposed to PCB 11, and demonstrate that environmentally relevant levels of PCB 11 alter axonal and dendritic growth in neuronal cell types critically involved in cognitive and higher-order behaviors. These findings identify PCB 11 as a potential environmental risk factor for adverse neurodevelopmental outcomes in humans.

Original languageEnglish (US)
Article numberkfx100
Pages (from-to)401-411
Number of pages11
JournalToxicological Sciences
Volume158
Issue number2
DOIs
StatePublished - Aug 1 2017

Fingerprint

Plasma (human)
Polychlorinated Biphenyls
Neurons
Rats
Mothers
Growth
Metabolites
3,3'-dichlorobiphenyl
Pyramidal Cells
Neocortex
Coculture Techniques
Morphogenesis
Pigments
Neuroglia

Keywords

  • Axonal growth
  • Cell culture
  • Dendritic growth
  • Developmental neurotoxicity
  • Exposure assessment
  • Polychlorinated biphenyls

ASJC Scopus subject areas

  • Toxicology

Cite this

Detection of 3,3'-Dichlorobiphenyl in human maternal plasma and its effects on axonal and dendritic growth in primary rat neurons. / Sethi, Sunjay; Keil, Kimberly P.; Chen, Hao; Hayakawa, Keri; Li, Xueshu; Lin, Yanping; Lehmler, Hans Joachim; Puschner, Birgit; Lein, Pamela J.

In: Toxicological Sciences, Vol. 158, No. 2, kfx100, 01.08.2017, p. 401-411.

Research output: Contribution to journalArticle

Sethi, Sunjay ; Keil, Kimberly P. ; Chen, Hao ; Hayakawa, Keri ; Li, Xueshu ; Lin, Yanping ; Lehmler, Hans Joachim ; Puschner, Birgit ; Lein, Pamela J. / Detection of 3,3'-Dichlorobiphenyl in human maternal plasma and its effects on axonal and dendritic growth in primary rat neurons. In: Toxicological Sciences. 2017 ; Vol. 158, No. 2. pp. 401-411.
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