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Lin, S.* ; Liu, H.* ; Kanawati, B. ; Liu, L.* ; Dong, J.* ; Li, M.* ; Huang, J.* ; Schmitt-Kopplin, P. ; Cai, Z.*

Hippocampal metabolomics using ultrahigh-resolution mass spectrometry reveals neuroinflammation from Alzheimer's disease in CRND8 mice.

Anal. Bioanal. Chem. 405, 5105-5117 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
In the wake of genomics, metabolomics characterizes the small molecular metabolites revealing the phenotypes induced by gene mutants. To address the metabolic signatures in the hippocampus of the amyloid-beta (Aβ) peptides produced in transgenic (Tg) CRND8 mice, high-field ion cyclotron resonance-Fourier transform mass spectrometry supported by LC-LTQ-Orbitrap was introduced to profile the extracted metabolites. More than 10,000 ions were detected in the mass profile for each sample. Subsequently, peak alignment and the 80 % rule followed by feature selection based on T score computation were performed. The putative identification was also conducted using the highly accurate masses with isotopic distribution by interfacing the MassTRIX database as well as MS/MS fragmentation generated in the LTQ-Orbitrap after chromatographic separation. Consequently, 58 differentiating masses were tentatively identified while up to 44 differentiating elemental compositions could not be biologically annotated in the databases. Nonetheless, of the putatively annotated masses, eicosanoids in arachidonic acid metabolism, fatty acid beta-oxidation disorders as well as disturbed glucose metabolism were highlighted as metabolic traits of Aβ toxicity in Tg CRND8 mice. Furthermore, a web-based bioinformatic tool was used for simulation of the metabolic pathways. As a result of the obtained metabolic signatures, the arachidonic acid metabolism dominates the metabolic perturbation in hippocampal tissues of Tg CRND8 mice compared to non-Tg littermates, indicating that Aβ toxicity functions neuroinflammation in hippocampal tissue and new theranostic opportunities might be offered by characterization of altered arachidonic acid metabolism for Alzheimer's disease.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Metabolomics; FTMS; Arachnoid acid metabolomics; Hippocampus; Alzheimer's disease; TRANSGENIC MOUSE MODEL; SWEDISH APP MUTATION; AMYLOID DEPOSITION; METABOLITE IDENTIFICATION; SECRETASE CLEAVAGE; FT-ICR; INFLAMMATION; DEFICITS
ISSN (print) / ISBN 1618-2642
e-ISSN 1618-2650
Journal Analytical and Bioanalytical Chemistry
Quellenangaben Volume: 405, Issue: 15, Pages: 5105-5117 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Heidelberg
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit BioGeoChemistry and Analytics (BGC)