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Cerebral Bioimaing 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)

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2010
Springer New York [u.a.]

Journal of the American Society for Mass Spectrometry 21, 161 - 171 () [10.1016/j.jasms.2009.09.022]

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Abstract: 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.

Keyword(s): 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: pharmacology (MeSH) ; Animals (MeSH) ; Brain: drug effects (MeSH) ; Brain: pathology (MeSH) ; Brain Chemistry (MeSH) ; Calibration (MeSH) ; Copper: analysis (MeSH) ; Equipment Design (MeSH) ; Iron: analysis (MeSH) ; Laser Therapy (MeSH) ; Male (MeSH) ; Manganese: analysis (MeSH) ; Mass Spectrometry: instrumentation (MeSH) ; Mass Spectrometry: methods (MeSH) ; Metals, Heavy: analysis (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Neurotoxins: pharmacology (MeSH) ; Parkinson Disease: metabolism (MeSH) ; Zinc: analysis (MeSH) ; Metals, Heavy ; Neurotoxins ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Iron ; Manganese ; Copper ; Zinc ; J


Note: The authors thank A. Zimmermann (Forschungszentrum Julich) for technical support with LA-ICP-MS measurements. This study was supported in part by the German Parkinson's Society and the University Hospitals of Giessen and Marburg, Germany.

Contributing Institute(s):
  1. Zentralabteilung für Chemische Analysen (ZCH)
  2. Strukturelle und funktionelle Organisation des Gehirns (INM-1)
  3. Molekulare Organisation des Gehirns (INM-2)
Research Program(s):
  1. Funktion und Dysfunktion des Nervensystems (FUEK409) (FUEK409)
  2. 89572 - (Dys-)function and Plasticity (POF2-89572) (POF2-89572)

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 Record created 2012-11-13, last modified 2021-01-29



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