Document Type

Journal Article

Department/Unit

Department of Chemistry

Title

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

Language

English

Abstract

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. [Figure not available: see fulltext.] © 2013 Springer-Verlag Berlin Heidelberg.

Keywords

Alzheimer's disease, Arachidonic acid metabolism, FTMS, Hippocampus, Metabolomics

Publication Date

2013

Source Publication Title

Analytical and Bioanalytical Chemistry

Volume

405

Issue

15

Start Page

5105

End Page

5117

Publisher

Springer Verlag

DOI

10.1007/s00216-013-6825-1

Link to Publisher's Edition

http://dx.doi.org/10.1007/s00216-013-6825-1

ISSN (print)

16182642

ISSN (electronic)

16182650

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