Neurotoxicity of polychlorinated biphenyls and related organohalogens.
Isaac N PessahPamela J LeinRichard F SeegalSharon K SagivPublished in: Acta neuropathologica (2019)
Halogenated organic compounds are pervasive in natural and built environments. Despite restrictions on the production of many of these compounds in most parts of the world through the Stockholm Convention on Persistent Organic Pollutants (POPs), many "legacy" compounds, including polychlorinated biphenyls (PCBs), are routinely detected in human tissues where they continue to pose significant health risks to highly exposed and susceptible populations. A major concern is developmental neurotoxicity, although impacts on neurodegenerative outcomes have also been noted. Here, we review human studies of prenatal and adult exposures to PCBs and describe the state of knowledge regarding outcomes across domains related to cognition (e.g., IQ, language, memory, learning), attention, behavioral regulation and executive function, and social behavior, including traits related to attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). We also review current understanding of molecular mechanisms underpinning these associations, with a focus on dopaminergic neurotransmission, thyroid hormone disruption, calcium dyshomeostasis, and oxidative stress. Finally, we briefly consider contemporary sources of organohalogens that may pose human health risks via mechanisms of neurotoxicity common to those ascribed to PCBs.
Keyphrases
- attention deficit hyperactivity disorder
- autism spectrum disorder
- endothelial cells
- working memory
- oxidative stress
- healthcare
- induced pluripotent stem cells
- pluripotent stem cells
- pregnant women
- type diabetes
- genome wide
- ischemia reperfusion injury
- mild cognitive impairment
- metabolic syndrome
- weight loss
- young adults
- drinking water