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Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?

1
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
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Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA
*
Authors to whom correspondence should be addressed.
Toxics 2020, 8(3), 70; https://doi.org/10.3390/toxics8030070
Received: 7 August 2020 / Revised: 14 September 2020 / Accepted: 16 September 2020 / Published: 17 September 2020
(This article belongs to the Special Issue Prenatal Environmental Exposure and Autism Risk)
Autism spectrum disorder (ASD) includes a group of multifactorial neurodevelopmental disorders defined clinically by core deficits in social reciprocity and communication, restrictive interests and repetitive behaviors. ASD affects one in 54 children in the United States, one in 89 children in Europe, and one in 277 children in Asia, with an estimated worldwide prevalence of 1–2%. While there is increasing consensus that ASD results from complex gene x environment interactions, the identity of specific environmental risk factors and the mechanisms by which environmental and genetic factors interact to determine individual risk remain critical gaps in our understanding of ASD etiology. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been linked to altered neurodevelopment in humans. Preclinical studies demonstrate that PCBs modulate signaling pathways implicated in ASD and phenocopy the effects of ASD risk genes on critical morphometric determinants of neuronal connectivity, such as dendritic arborization. Here, we review human and experimental evidence identifying PCBs as potential risk factors for ASD and discuss the potential for PCBs to influence not only core symptoms of ASD, but also comorbidities commonly associated with ASD, via effects on the central and peripheral nervous systems, and/or peripheral target tissues, using bladder dysfunction as an example. We also discuss critical data gaps in the literature implicating PCBs as ASD risk factors. Unlike genetic factors, which are currently irreversible, environmental factors are modifiable risks. Therefore, data confirming PCBs as risk factors for ASD may suggest rational approaches for the primary prevention of ASD in genetically susceptible individuals. View Full-Text
Keywords: axons; bladder dysfunction; dendritic arborization; dendritic spines; calcium signaling; neuronal connectivity; persistent organic pollutants; ryanodine receptor; synapses axons; bladder dysfunction; dendritic arborization; dendritic spines; calcium signaling; neuronal connectivity; persistent organic pollutants; ryanodine receptor; synapses
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Panesar, H.K.; Kennedy, C.L.; Keil Stietz, K.P.; Lein, P.J. Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder? Toxics 2020, 8, 70.

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