The neurotoxic effect of manganese (Mn) establishes itself in a condition known as manganism or Mn induced\r\nparkinsonism. While this condition was first diagnosed about 170 years ago, the mechanism of the neurotoxic action of Mn\r\nremains unknown. Moreover, the possibility that Mn exposure combined with other genetic and environmental factors can\r\ncontribute to the development of Parkinson�s disease has been discussed in the literature and several epidemiological\r\nstudies have demonstrated a correlation between Mn exposure and an elevated risk of Parkinson�s disease. Here, we\r\nintroduce X-ray fluorescence imaging as a new quantitative tool for analysis of the Mn distribution in the brain with high\r\nspatial resolution. The animal model employed mimics deficits observed in affected human subjects. The obtained maps of\r\nMn distribution in the brain demonstrate the highest Mn content in the globus pallidus, the thalamus, and the substantia\r\nnigra pars compacta. To test the hypothesis that Mn transport into/distribution within brain cells mimics that of other\r\nbiologically relevant metal ions, such as iron, copper, or zinc, their distributions were compared. It was demonstrated that\r\nthe Mn distribution does not follow the distributions of any of these metals in the brain. The majority of Mn in the brain was\r\nshown to occur in the mobile state, confirming the relevance of the chelation therapy currently used to treat Mn\r\nintoxication. In cells with accumulated Mn, it can cause neurotoxic action by affecting the mitochondrial respiratory chain.\r\nThis can result in increased susceptibility of the neurons of the globus pallidus, thalamus, and substantia nigra pars\r\ncompacta to various environmental or genetic insults. The obtained data is the first demonstration of Mn accumulation in\r\nthe substantia nigra pars compacta, and thus, can represent a link between Mn exposure and its potential effects for\r\ndevelopment of Parkinson�s disease.
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