期刊
TOXICOLOGICAL SCIENCES
卷 158, 期 2, 页码 401-411出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfx100
关键词
axonal growth; cell culture; dendritic growth; developmental neurotoxicity; exposure assessment; polychlorinated biphenyls
类别
资金
- National Institute of Environmental Health [R01 ES014901, R01 ES017425, P30 ES023513, P42 ES013661, P01 ES011269, T32 ES007059]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [U54 HD079125, F32 HD088016]
- United States Environmental Protection Agency [RD 83543201]
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 (mu M) 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 similar to 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.
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