Cargando…
X-Ray Fluorescence Imaging: A New Tool for Studying Manganese Neurotoxicity
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 wit...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501493/ https://www.ncbi.nlm.nih.gov/pubmed/23185282 http://dx.doi.org/10.1371/journal.pone.0048899 |
_version_ | 1782250199294410752 |
---|---|
author | Robison, Gregory Zakharova, Taisiya Fu, Sherleen Jiang, Wendy Fulper, Rachael Barrea, Raul Marcus, Matthew A. Zheng, Wei Pushkar, Yulia |
author_facet | Robison, Gregory Zakharova, Taisiya Fu, Sherleen Jiang, Wendy Fulper, Rachael Barrea, Raul Marcus, Matthew A. Zheng, Wei Pushkar, Yulia |
author_sort | Robison, Gregory |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3501493 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35014932012-11-26 X-Ray Fluorescence Imaging: A New Tool for Studying Manganese Neurotoxicity Robison, Gregory Zakharova, Taisiya Fu, Sherleen Jiang, Wendy Fulper, Rachael Barrea, Raul Marcus, Matthew A. Zheng, Wei Pushkar, Yulia PLoS One Research Article 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. Public Library of Science 2012-11-19 /pmc/articles/PMC3501493/ /pubmed/23185282 http://dx.doi.org/10.1371/journal.pone.0048899 Text en © 2012 Robison et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Robison, Gregory Zakharova, Taisiya Fu, Sherleen Jiang, Wendy Fulper, Rachael Barrea, Raul Marcus, Matthew A. Zheng, Wei Pushkar, Yulia X-Ray Fluorescence Imaging: A New Tool for Studying Manganese Neurotoxicity |
title | X-Ray Fluorescence Imaging: A New Tool for Studying Manganese Neurotoxicity |
title_full | X-Ray Fluorescence Imaging: A New Tool for Studying Manganese Neurotoxicity |
title_fullStr | X-Ray Fluorescence Imaging: A New Tool for Studying Manganese Neurotoxicity |
title_full_unstemmed | X-Ray Fluorescence Imaging: A New Tool for Studying Manganese Neurotoxicity |
title_short | X-Ray Fluorescence Imaging: A New Tool for Studying Manganese Neurotoxicity |
title_sort | x-ray fluorescence imaging: a new tool for studying manganese neurotoxicity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501493/ https://www.ncbi.nlm.nih.gov/pubmed/23185282 http://dx.doi.org/10.1371/journal.pone.0048899 |
work_keys_str_mv | AT robisongregory xrayfluorescenceimaginganewtoolforstudyingmanganeseneurotoxicity AT zakharovataisiya xrayfluorescenceimaginganewtoolforstudyingmanganeseneurotoxicity AT fusherleen xrayfluorescenceimaginganewtoolforstudyingmanganeseneurotoxicity AT jiangwendy xrayfluorescenceimaginganewtoolforstudyingmanganeseneurotoxicity AT fulperrachael xrayfluorescenceimaginganewtoolforstudyingmanganeseneurotoxicity AT barrearaul xrayfluorescenceimaginganewtoolforstudyingmanganeseneurotoxicity AT marcusmatthewa xrayfluorescenceimaginganewtoolforstudyingmanganeseneurotoxicity AT zhengwei xrayfluorescenceimaginganewtoolforstudyingmanganeseneurotoxicity AT pushkaryulia xrayfluorescenceimaginganewtoolforstudyingmanganeseneurotoxicity |