Cerebral Bioimaging of Cu, Fe, Zn, and Mn in the MPTP Mouse Model of Parkinson's Disease Using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS)

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been established as a powerful technique for the determination of metal and nonmetal distributions within biological systems with high sensitivity. An imaging LA-ICP-MS technique for Fe, Cu, Zn, and Mn was developed to produ...

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Bibliographic Details
Published in:Journal of the American Society for Mass Spectrometry 2010, Vol.21 (1), p.161-171
Main Authors: Matusch, Andreas, Depboylu, Candan, Palm, Christoph, Wu, Bei, Höglinger, Günter U., Schäfer, Martin K.-H., Becker, J. Sabine
Format: Article
Language:English
Subjects:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology
Analytical Chemistry
Animals
Bioinformatics
Biotechnology
Brain
Brain - drug effects
Brain - pathology
Brain Chemistry
Calibration
Chemistry
Chemistry and Materials Science
Copper
Copper - analysis
Emission spectroscopy
Equipment Design
Inductively coupled plasma mass spectrometry
Iron - analysis
Laser ablation
Laser Therapy
Male
Manganese
Manganese - analysis
Mass spectrometry
Mass Spectrometry - instrumentation
Mass Spectrometry - methods
Medical imaging
Metals, Heavy - analysis
Mice
Mice, Inbred C57BL
Neurotoxins - pharmacology
Organic Chemistry
Parkinson Disease - metabolism
Parkinson's disease
Proteomics
Scientific imaging
Zinc
Zinc - analysis
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Summary:Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been established as a powerful technique for the determination of metal and nonmetal distributions within biological systems with high sensitivity. An imaging LA-ICP-MS technique for Fe, Cu, Zn, and Mn was developed to produce large series of quantitative element maps in native brain sections of mice subchronically intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) as a model of Parkinson's disease. Images were calibrated using matrix-matched laboratory standards. A software solution allowing a precise delineation of anatomical structures was implemented. Coronal brain sections were analyzed crossing the striatum and the substantia nigra, respectively. Animals sacrificed 2 h, 7 d, or 28 d after the last MPTP injection and controls were investigated. We observed significant decreases of Cu concentrations in the periventricular zone and the fascia dentata at 2 h and 7d and a recovery or overcompensation at 28 d, most pronounced in the rostral periventricular zone (+40%). In the cortex Cu decreased slightly to −10%. Fe increased in the interpeduncular nucleus (+40%) but not in the substantia nigra. This pattern is in line with a differential regulation of periventricular and parenchymal Cu, and with the histochemical localization of Fe, and congruent to regions of preferential MPTP binding described in the rodent brain. The LA-ICP-MS technique yielded valid and statistically robust results in the present study on 39 slices from 19 animals. Our findings underline the value of routine micro-local analytical techniques in the life sciences and affirm a role of Cu availability in Parkinson's disease. Quantitation in 18 animals showed a time profile of periventricular Cu paralleling the course of classical dopaminergic markers at 2 h, 7 d, and 28 d.
ISSN:1044-0305
1879-1123
DOI:10.1016/j.jasms.2009.09.022