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X-Ray Fluorescence Imaging: A New Tool for Studying Manganese Neurotoxicity

Journal Article · · PLoS ONE
 [1];  [2];  [3];  [3];  [2];  [4];  [5];  [3];  [2]
  1. Purdue Univ., West Lafayette, IN (United States). Dept. of Physics; DOE/OSTI
  2. Purdue Univ., West Lafayette, IN (United States). Dept. of Physics
  3. Purdue Univ., West Lafayette, IN (United States). School of Health Sciences
  4. Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)
The neurotoxic effect of manganese (Mn) establishes itself in a condition known as manganism or Mn induced parkinsonism. 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.
Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231; AC02-06CH11357
OSTI ID:
1627557
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 11 Vol. 7; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (7)

Visualizing Metal Content and Intracellular Distribution in Primary Hippocampal Neurons with Synchrotron X-Ray Fluorescence journal July 2016
Manganese Toxicity Upon Overexposure: a Decade in Review journal July 2015
X-ray fluorescence imaging of the hippocampal formation after manganese exposure journal January 2013
Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry journal January 2018
Elevated Adult Neurogenesis in Brain Subventricular Zone Following In vivo Manganese Exposure: Roles of Copper and DMT1 journal January 2015
Subchronic Manganese Exposure Impairs Neurogenesis in the Adult Rat Hippocampus journal March 2018
Mapping Chemical Elements and Iron Oxidation States in the Substantia Nigra of 6-Hydroxydopamine Lesioned Rats Using Correlative Immunohistochemistry With Proton and Synchrotron Micro-Analysis journal September 2019

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