Objective: To investigate the impact of dioxins on movement disorder development and the mechanisms increasing vulnerability to future motor dysfunction.

Background: Dioxins are persistent organic pollutants that act via the aryl hydrocarbon receptor (AhR) pathway, which is implicated in nigrostriatal damage, oxidative stress, and neuroinflammation. Dioxins have the potential to disrupt dopaminergic neuron development with potential long-term consequences for basal ganglia function and movement disorders. This review synthesizes evidence linking perinatal exposure to dioxins to dopamine system dysfunction, dystonia, and early-onset Parkinsonian features.

Method: A narrative review of longitudinal cohort studies and animal experimental neurotoxicological research was conducted which evaluated perinatal dioxin exposure levels and association with  motor development (rigidity, bradykinesia, tremor and dystonic features), neuroimaging/electrophysiological evidence of altered basal ganglia function following early-life exposure, and insights from animal models that link AhR activation to persistent dysfunction in the dopaminergic system and increased susceptibility to Parkinson’s disease.

Results: Evidence linking dioxin exposure to movement disorders is mixed. Some cohort studies report high perinatal exposure correlates with motor coordination impairments and altered striatal dopamine receptor density, particularly in male offspring. However, other longitudinal studies find no significant association with later-life motor dysfunction, suggesting resilience mechanisms. Animal studies show high-dose perinatal dioxin exposure induces persistent dopaminergic dysfunction, but effects vary by dose and species. The role of confounders, such as co-exposure to neurotoxicants (e.g., heavy metals, pesticides) and genetic predispositions, remains underexplored in human studies.

Conclusion: Preclinical data suggest high-dose perinatal dioxin exposure can disrupt dopaminergic signaling and increase neurodegeneration risk, but epidemiological evidence does not confirm a definitive causal link to human movement disorders. Given dioxins’ environmental persistence, ongoing monitoring of exposure and neurodevelopmental effects is warranted.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/perinatal-dioxin-exposure-and-dopaminergic-vulnerability-in-the-development-of-motor-dysfunction-sequelae/