The epigenetic mechanisms mediating the long-term impacts of toxicants on brain functions and health.

Recent advances in toxicoepigenetics have significantly enhanced our understanding of epigenetic modifications induced by toxicant exposures. This review synthesizes current knowledge regarding epigenetic alterations - primarily DNA methylation, histone acetylation, and miRNA perturbations - associated with common toxicants, including arsenic, lead, methylmercury, formaldehyde, α-hexabromocyclododecane, bisphenol A, and fluoxetine. While substantial evidence derives from rodent models, human studies have made crucial contributions by characterizing toxicant-specific epigenetic signatures, identifying affected genes and pathways, and establishing epigenetic regulation as a critical mediator of biologic responses. This review highlights parallels between toxicant-induced epigenetic changes and those observed in neurologic disorders, particularly focusing on the potential of epigenetic marks as early diagnostic tools for synaptic dysfunction in Alzheimer disease, but also focusing on Huntington disease and Parkinson disease. It relies on evidence ranging from exposures in vitro and in vivo (mainly in rodents) to human exposures. It also highlights parallels between toxicant-induced epigenetic changes and those observed in brain cancers. The findings underscore the therapeutic potential of targeting epigenetic mechanisms to mitigate toxicant-induced neurologic effects. We conclude by proposing a strategic framework for further advancing toxicoepigenetic research, emphasizing the creation of a centralized databank for toxicant-induced brain epigenetic alterations, the development of validated epigenetic bioassays, and the integration of functional neuroimaging. Our proposed comprehensive approach, combining genetics, toxicology, epidemiology, and environmental science, aims to inform and enhance risk assessment protocols and therapeutic interventions.