X-ray fluorescence imaging: a new tool for studying manganese neurotoxicity
| Autor: | Matthew A. Marcus, Rachael Fulper, Yulia Pushkar, Sherleen Fu, Wei Zheng, Gregory Robison, Wendy Jiang, Taisiya Zakharova, Raúl A. Barrea |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Pathology
lcsh:Medicine Neural Homeostasis Toxicology 0302 clinical medicine Manganism lcsh:Science 0303 health sciences Multidisciplinary Physics Electromagnetic Radiation Parkinsonism Dopaminergic Brain Parkinson Disease Zinc Chemistry Globus pallidus Mitochondrial respiratory chain Neurology Medicine Research Article Diagnostic Imaging Neurotoxicology medicine.medical_specialty Iron Neurotoxins Toxic Agents Biophysics Neuroimaging Substantia nigra Biology Fluorescence 03 medical and health sciences medicine Animals Humans 030304 developmental biology Manganese Chemical Physics Pars compacta X-Rays lcsh:R Neurotoxicity medicine.disease Rats Disease Models Animal nervous system lcsh:Q Copper 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | PLoS ONE, Vol 7, Iss 11, p e48899 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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