Evidence Implicating Non-Dioxin-Like Congeners as the Key Mediators of Polychlorinated Biphenyl (PCB) Developmental Neurotoxicity

International Journal of Molecular Sciences

PamelaJ. Lein¹  Carolyn Klocke¹ 

[1] Department of Molecular Biosciences, University of California, Davis, School of Veterinary Medicine, Davis, CA 95616, USA;

关键词: arylhydrocarbon receptor (ahr);    creb signaling;    dendritic arborization;    developmental neurotoxicity;    neurodevelopmental disorders;    polychlorinated biphenyls;    pcbs;    ryanodine receptor (ryr), thyroid hormone receptor (thr);   

DOI  :  10.3390/ijms21031013

来源: DOAJ

【 摘 要 】

Despite being banned from production for decades, polychlorinated biphenyls (PCBs) continue to pose a significant risk to human health. This is due to not only the continued release of legacy PCBs from PCB-containing equipment and materials manufactured prior to the ban on PCB production, but also the inadvertent production of PCBs as byproducts of contemporary pigment and dye production. Evidence from human and animal studies clearly identifies developmental neurotoxicity as a primary endpoint of concern associated with PCB exposures. However, the relative role(s) of specific PCB congeners in mediating the adverse effects of PCBs on the developing nervous system, and the mechanism(s) by which PCBs disrupt typical neurodevelopment remain outstanding questions. New questions are also emerging regarding the potential developmental neurotoxicity of lower chlorinated PCBs that were not present in the legacy commercial PCB mixtures, but constitute a significant proportion of contemporary human PCB exposures. Here, we review behavioral and mechanistic data obtained from experimental models as well as recent epidemiological studies that suggest the non-dioxin-like (NDL) PCBs are primarily responsible for the developmental neurotoxicity associated with PCBs. We also discuss emerging data demonstrating the potential for non-legacy, lower chlorinated PCBs to cause adverse neurodevelopmental outcomes. Molecular targets, the relevance of PCB interactions with these targets to neurodevelopmental disorders, and critical data gaps are addressed as well.

【 授权许可】

Unknown