Integrating exposure across the lifespan: Early life exposures as risk factors for Parkinson's disease.
Integrating exposure across the lifespan: Early life exposures as risk factors for Parkinson's disease.
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Original abstract
Environmental risk factors and gene-environment interactions play critical roles in Parkinson's disease (PD) pathogenesis, and approximately two-thirds of the phenotypic variance of sporadic PD appears to be attributed to non-heritable factors. The majority of research on environmental risk factors in PD is focused on adult exposures, largely reliant on recall from occupational or lifestyle factors. However, because PD is a progressive disorder with prolonged preclinical and prodromal phases, exposures that contribute to PD risk are likely to occur long before symptom onset, including during early life. According to the developmental origins of health and disease (DoHAD) hypothesis, exposures that occur at critical periods of neurodevelopment can produce long-lasting changes that contribute to neurological disease. While these effects are studied mainly in the context of neurodevelopmental disorders, these effects can persist to affect risk for late-onset disease. Here, we review existing literature on the impact of developmental and early-life exposures to well-established PD-related toxicants to assess the state and rigor of the extant literature and highlight the need for future studies to evaluate the impact of early-life exposures to specific toxicants across the lifespan, particularly for later-life neurodegeneration. Overall, existing data shows that, in addition to their adult neurotoxicity, PD-related toxicants also produce persistent developmental neurotoxicity. However, a "neurodegeneration gap" exists as few developmental studies have evaluated dopaminergic dysfunction specifically, neurodegeneration-relevant outcomes, or the effects of aging. In addition, the existing literature is plagued by methodological and reporting issues that limit interpretation and hinder progress in this field. Future research must prioritize standardized reporting, environmentally relevant dosing, and the incorporation of aging to determine if these early life exposures contribute to persistent and latent neurotoxicity relevant to PD.