Manganese (Mn) is an essential element required in trace amounts for proper body function. However, despite its vital role in enzymatic reactions, excessive Mn exposure leads to a condition known as manganism or Mn induced parkinsonism. Clinical signs and symptoms of manganism closely resemble those of Parkinson’s disease (PD) and both diseases are pathologically associated with damage to the basal ganglia. While this condition was first diagnosed about 170 years ago, the mechanism of the neurotoxic action of Mn remains unknown. Moreover, the possibility that Mn exposure combined with other genetic and environmental factors can contribute to the development of Parkinson’s disease has been discussed in the literature and several epidemiological studies have demonstrated a correlation between Mn exposure and an elevated risk of Parkinson’s disease. Here, we introduce X-ray fluorescence imaging as a new quantitative tool for analysis of the Mn distribution in the brain with high spatial resolution. The animal model employed mimics deficits observed in affected human subjects. The obtained maps of Mn distribution in the brain demonstrate the highest Mn content in the globus pallidus, the thalamus, and the substantia nigra pars compacta. To test the hypothesis that Mn transport into/distribution within brain cells mimics that of other biologically relevant metal ions, such as iron, copper, or zinc, their distributions were compared. It was demonstrated that the Mn distribution does not follow the distributions of any of these metals in the brain. The majority of Mn in the brain was shown to occur in the mobile state, confirming the relevance of the chelation therapy currently used to treat Mn intoxication. In cells with accumulated Mn, it can cause neurotoxic action by affecting the mitochondrial respiratory chain. This can result in increased susceptibility of the neurons of the globus pallidus, thalamus, and substantia nigra pars compacta to various environmental or genetic insults. The obtained data is the first demonstration of Mn accumulation in the substantia nigra pars compacta, and thus, can represent a link between Mn exposure and its potential effects for development of Parkinson’s disease.
Citation: Gregory Robison, Taisiya Zakharova, Sherleen Fu, Wendy Jiang, Rachael Fulper, Raul Barrea, Matthew A. Marcus, Wei Zheng, and Yulia Pushkar (2012) X-Ray Fluorescence Imaging: A New Tool for Studying Manganese Neurotoxicity. PLoS ONE 7(11): e48899. doi:10.1371/journal.pone.0048899 PMCID:PMC3501493
The Pushkar collaboration is one of the success stories of our XFM developments leading to two publications in 2012. A relative latecomer to our facility she is making excellent use of our existing scanning diffraction imaging capabilities in combination with XFM. She provides a Driving Biomedical Project for our planned future developments.