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 language | English (US) |
|---|---|
| Article number | kfx100 |
| Pages (from-to) | 401-411 |
| Number of pages | 11 |
| Journal | Toxicological Sciences |
| Volume | 158 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 1 2017 |
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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 journal › Article
}
TY - JOUR
T1 - Detection of 3,3'-Dichlorobiphenyl in human maternal plasma and its effects on axonal and dendritic growth in primary rat neurons
AU - Sethi, Sunjay
AU - Keil, Kimberly P.
AU - Chen, Hao
AU - Hayakawa, Keri
AU - Li, Xueshu
AU - Lin, Yanping
AU - Lehmler, Hans Joachim
AU - Puschner, Birgit
AU - Lein, Pamela J
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
KW - Axonal growth
KW - Cell culture
KW - Dendritic growth
KW - Developmental neurotoxicity
KW - Exposure assessment
KW - Polychlorinated biphenyls
UR - http://www.scopus.com/inward/record.url?scp=85028344348&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028344348&partnerID=8YFLogxK
U2 - 10.1093/toxsci/kfx100
DO - 10.1093/toxsci/kfx100
M3 - Article
C2 - 28510766
AN - SCOPUS:85028344348
VL - 158
SP - 401
EP - 411
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 2
M1 - kfx100
ER -