1654b Manganese toxicity across the lifespan from prenatal exposure to the old age

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IntroductionManganese exposure causes neurotoxicity from prenatal life to the old age. An extended body of literature is now available on:different exposure sources and routes of absorption;mechanistic aspects provided also by imaging assessment;dose–response relationship from epidemiological and animal studies;gender differences;genetic predisposition.MethodsNew evidence was reviewed from the scientific literature and the studies presented during the world conference held in 2016 at the Icahn School of Medicine at Mount Sinai, New York, USA.ResultsCurrent manganese research offers a wide spectrum of observations within a continuum of exposure from early life to old age, with new evidence of neurotoxicity at low exposure levels in occupational settings and operations including welding. Gender differences are consistently shown by human studies and toxicity vs beneficial effects are reported to varying as a function of the exposure windows. Brain imaging studies through structural and functional MRI provide new information about differences and similarities between occupational, environmental exposure and parkinsonian conditions. Genetic studies focused on genes regulating specific transporters, such as SLC30A10, offer new prospective in understanding the regulation of metabolic pathway and toxico-dinamic properties of manganese.ConclusionManganese exposure is increasingly common through a variety of industrial and agricultural products. Current research offers consistent evidence of potential links from neurodevelopment to neurodegeneration. The enhanced vulnerability of specific exposure windows and the cumulative mechanism of toxicity require further studies to identify the critical windows of susceptibility and the exposure levels suitable to protect the brain throughout the lifetime exposure. Understanding these aspects is of outmost relevance in view of the potential role of manganese as determinant of both neurodevelopmental disorders and neurodegenerative diseases.

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