# Polychlorinated Biphenyls, Oxidative Stress, and Brain Health: Mechanistic Links to Neurodegenerative and Neurodevelopmental Diseases

## TL;DR

This paper reviews how polychlorinated biphenyls (PCBs) harm brain health by causing oxidative stress and other cellular disruptions, leading to neurodevelopmental and neurodegenerative diseases.

## Contribution

The paper provides a comprehensive synthesis of PCB-induced neurotoxicity mechanisms, emphasizing oxidative stress as a central factor across the lifespan.

## Key findings

- PCBs disrupt neuronal function through oxidative stress, calcium dysregulation, and epigenetic changes.
- Developmental PCB exposure is linked to cognitive and motor impairments and neurodevelopmental disorders.
- Chronic PCB exposure in adulthood is associated with neurodegenerative diseases via mitochondrial dysfunction and neuroinflammation.

## Abstract

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that remain widely detectable in the environment and human tissues decades after their ban, raising concerns for brain health. Both dioxin-like (DL) and non-dioxin-like (NDL) congeners interfere with neuronal function through partially distinct pathways, including aryl hydrocarbon receptor activation, disruption of calcium and dopaminergic signaling, oxidative stress, and epigenetic remodeling. Experimental and epidemiological studies indicate that developmental PCB exposure is associated with impaired cognition, attention, motor function, and increased risk of neurodevelopmental disorders. Furthermore, chronic exposure in adulthood has been linked to neurodegenerative diseases. At the cellular level, NDL-PCBs sensitize ryanodine receptors, alter dendritic and axonal growth, promote mitochondrial dysfunction, generate reactive oxygen and nitrogen species, and compromise blood–brain barrier integrity, thereby fostering neuroinflammation, synaptic dysfunction, and neuronal loss. This review synthesizes current evidence on the molecular and cellular mechanismtable s underlying PCB-induced neurotoxicity across the lifespan, highlighting oxidative stress as a central factor, integrating calcium dysregulation, neurotransmitter imbalance, and apoptotic and epigenetic pathways. Finally, potential neuroprotective roles of antioxidant strategies are discussed, emphasizing their relevance for mitigating PCB-related neurodevelopmental and neurodegenerative risk.