title: 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).
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.
authors.affiliation: Institute of Neurosciences and Medicine (INM-1 and -2), Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Matusch
authors.forename: Candan
authors.initials: C
authors.lastname: Depboylu
authors.forename: Christoph
authors.initials: C
authors.lastname: Palm
authors.forename: Bei
authors.initials: B
authors.lastname: Wu
authors.forename: Günter U
authors.initials: GU
authors.lastname: Höglinger
authors.forename: Martin K-H
authors.initials: MK
authors.lastname: Schäfer
authors.forename: J Sabine
authors.initials: JS
authors.lastname: Becker
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001923:Brain Chemistry; D002138:Calibration; D003300:Copper / Q000032:analysis; D004867:Equipment Design; D007501:Iron / Q000032:analysis; D053685:Laser Therapy; D008297:Male; D008345:Manganese / Q000032:analysis; D013058:Mass Spectrometry / Q000295:instrumentation* / Q000379:methods*; D019216:Metals, Heavy / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000494:pharmacology; D010300:Parkinson Disease / Q000378:metabolism*; D015032:Zinc / Q000032:analysis
chemical_list: D019216:Metals, Heavy; D009498:Neurotoxins; D008345:Manganese; D003300:Copper; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D007501:Iron; D015032:Zinc