title: Changes in Brain Metallome/Metabolome Pattern due to a Single i.v. Injection of Manganese in Rats.
abstract: Exposure to high concentrations of Manganese (Mn) is known to potentially induce an accumulation in the brain, leading to a Parkinson related disease, called manganism. Versatile mechanisms of Mn-induced brain injury are discussed, with inactivation of mitochondrial defense against oxidative stress being a major one. So far, studies indicate that the main Mn-species entering the brain are low molecular mass (LMM) compounds such as Mn-citrate. Applying a single low dose MnCl2 injection in rats, we observed alterations in Mn-species pattern within the brain by analysis of aqueous brain extracts by size-exclusion chromatography--inductively coupled plasma mass spectrometry (SEC-ICP-MS). Additionally, electrospray ionization--ion cyclotron resonance-Fourier transform-mass spectrometry (ESI-ICR/FT-MS) measurement of methanolic brain extracts revealed a comprehensive analysis of changes in brain metabolisms after the single MnCl2 injection. Major alterations were observed for amino acid, fatty acid, glutathione, glucose and purine/pyrimidine metabolism. The power of this metabolomic approach is the broad and detailed overview of affected brain metabolisms. We also correlated results from the metallomic investigations (Mn concentrations and Mn-species in brain) with the findings from metabolomics. This strategy might help to unravel the role of different Mn-species during Mn-induced alterations in brain metabolism.
authors.affiliation: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München-German Research Center for Environment and Health (GmbH), Ingolstädter Landstrasse 1, D-85764, Neuherberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Neth
authors.affiliation: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München-German Research Center for Environment and Health (GmbH), Ingolstädter Landstrasse 1, D-85764, Neuherberg, Germany.
authors.forename: Marianna
authors.initials: M
authors.lastname: Lucio
authors.affiliation: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München-German Research Center for Environment and Health (GmbH), Ingolstädter Landstrasse 1, D-85764, Neuherberg, Germany.
authors.forename: Alesia
authors.initials: A
authors.lastname: Walker
authors.affiliation: Research Unit Comparative Medicine, Helmholtz Zentrum München-German Research Center for Environment and Health (GmbH), Ingolstädter Landstrasse 1, D-85764, Neuherberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Zorn
authors.affiliation: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München-German Research Center for Environment and Health (GmbH), Ingolstädter Landstrasse 1, D-85764, Neuherberg, Germany; Chair of Analytical Food Chemistry, Technische Universität München, Alte Akademie 10, D- 85354, Freising-Weihenstephan, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Schmitt-Kopplin
authors.affiliation: Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München-German Research Center for Environment and Health (GmbH), Ingolstädter Landstrasse 1, D-85764, Neuherberg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Michalke
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D002457:Cell Extracts / Q000737:chemistry; D002850:Chromatography, Gel; D005243:Feces / Q000737:chemistry; D007275:Injections, Intravenous; D008297:Male; D008345:Manganese / Q000008:administration & dosage / Q000494:pharmacology*; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods; D008670:Metals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D002457:Cell Extracts; D008670:Metals; D008345:Manganese