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Manganese is an essential mineral required for normal growth and development.Exposure to high Mn concentrations results in destructive symmetrical lesions in the basal ganglia, particularly in the globus pallidus (GP), a disease referred to as manganism;it shares multiple features with Parkinsons disease (PD).Combining genetics and biochemical assays, we established in the nematode (C elegans) that dopamine (DA) is responsible for Mn-induced DAergic neurodegeneration and that this process (1) requires functional DA-reuptake transporter (DAT-1) and (2)is associated with oxidative stress and lifespan reduction.Additional studies tested whether parenteral nutrition, PN (which is routinely supplemented with Mn) and liver disease represent risk factors for increased Mn brain deposition in human neonates.Brain Mn was assesed by T1 relaxation (T1 R) times (using magnetic resonance imaging;MRI) focusing on the GP.Brain Mn and its relationship to total dietary Mn, total days on PN, conjugated bilirubin levels and blood Mn concentrations was determined.Dietary Mn exposure was found to be inversely associated with GP T1 R.The results establish that T1-weighted MRI can be used to screen infants on prolonged PN for increased brain Mn deposition.Hepatic cholestasis was also found to represent a risk factor for increased brain Mn deposition in neonates receiving PN.Combined our data suggest that some infants receiving prolonged PN may be at risk for Mn neurotoxicity.