Metallomics and metabolomics studies in cerebrospinal fluid (CSF) of Parkinson´s disease (PD) patients: Cu-aminoacids and lipid peroxidation are cause for oxidative stressName : Bernhard Michalke
Affliation : Professor
University : Helmholtz Zentrum München
Country : Germany
Etiology of PD is incomplete understood, but occupational and environmental exposure to redox-active-metals (Fe,Mn,Cu,Zn), i.e. some of their specific binding forms (metal-species) and various metabolites influence PD-risk.
In this case-control study, we investigated the Mn-, Fe-,Cu- and Zn-species in CSF by size-exclusion-chromatography – inductively-coupled-plasma mass spectrometry (SEC-ICP-MS). In parallel, we performed non-targeted metabolomics studies using Fourier-transform-ion cycling resonance-mass spectrometry (FT-ICR-MS). Statistics: Multivariate statistical analyses were used for differentiation. Among others Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) and Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA) model yielded in good group separation.
In PD-CSF-samples, we monitored significantly increased ratios with enumerator being either total Fe, or total Zn, or Mn- and Zn-low molecular-weight-compounds, versus denominator throughout being Cu-carrying amino-acids. Overall 20 ratios showed significant increase in PD. Metabolomics analysis revealed 68 metabolites decreased and 152 metabolites increased in PD samples. Predominantly compounds from lipid metabolism (e.g. decanoic acid, 10-hydroxydecanoic-acid, arachidonic-acid, dihomo-γ-linolenic-acid) were affected in PD. Redox metabolism with Cu-amino-acids as key-player and lipid peroxidation appeared as major causes inducing oxidative stress in PD patients.
Redox active metal species play an important role in misbalanced metal ratios with Cu-amino-acid-fraction being crucial in PD etiology. We found many metabolites changed in CSF of Parkinson´s patients compared to controls when using non-targeted metabolomics technique FT-ICR-MS. Molecules of the lipid metabolism were affected in CSF of PD patients.
Bernhard Michalke is leader of the research group "Elements and Element Speciation" and of the "Central Inorganic Analysis Division" as well as deputy director of the Research Unit “Analytical BioGeoChemistry” at the Helmholtz Zentrum München– German Research Center for Environmental Health.
Bernhard received his diploma for biology in 1985 and his Ph.D. in 1988 from the Technical University of Munich. Since 1996 he has been lecturer at the "Institute of Analytical Chemistry and Foodchemistry" of the Technical University of Graz, Austria, where he also received his habilitation in analytical chemistry in 1999. Since 1988 Bernhard is principal researcher at the Helmholtz Zentrum München.
Bernhard is Head of the Advisory Board (former president 2004-2016) of the German Society on Minerals and Trace Elements (GMS). He is focusing on speciation projects (metallomics and metabolomics) related to environmental health, i.e. the exposure and chemical speciation of neuro-degenerative compounds and related neuro-toxic effects in the central nervous system. Bernhard has published more than 200 peer reviewed articles and 10 book chapters.