Metabolomic screening of regional brain alterations in the APP/PS1 transgenic model of Alzheimer's disease by direct infusion mass spectrometry

Raúl González-Domínguez; Tamara García-Barrera; Javier Vitorica; José Luis Gómez-Ariza

doi:10.1016/j.jpba.2014.10.009

Metabolomic screening of regional brain alterations in the APP/PS1 transgenic model of Alzheimer's disease by direct infusion mass spectrometry

J Pharm Biomed Anal. 2015 Jan:102:425-35. doi: 10.1016/j.jpba.2014.10.009. Epub 2014 Oct 22.

Authors

Raúl González-Domínguez¹, Tamara García-Barrera², Javier Vitorica³, José Luis Gómez-Ariza⁴

Affiliations

¹ Department of Chemistry and CC.MM, Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, 21007 Huelva, Spain; Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007 Huelva, Spain.
² Department of Chemistry and CC.MM, Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, 21007 Huelva, Spain; Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007 Huelva, Spain. Electronic address: tamara@dqcm.uhu.es.
³ Department Bioquímica, Bromatologia, Toxicología y Medicina Legal, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 41013 Seville, Spain; Instituto de Biomedicina de Sevilla (IBiS) - Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41013 Seville, Spain.
⁴ Department of Chemistry and CC.MM, Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, 21007 Huelva, Spain; Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007 Huelva, Spain. Electronic address: ariza@uhu.es.

PMID: 25459942
DOI: 10.1016/j.jpba.2014.10.009

Abstract

The identification of pathological mechanisms underlying to Alzheimer's disease is of great importance for the discovery of potential markers for diagnosis and disease monitoring. In this study, we investigated regional metabolic alterations in brain from the APP/PS1 mice, a transgenic model that reproduces well some of the neuropathological and cognitive deficits observed in human Alzheimer's disease. For this purpose, hippocampus, cortex, cerebellum and olfactory bulbs were analyzed using a high-throughput metabolomic approach based on direct infusion mass spectrometry. Metabolic fingerprints showed significant differences between transgenic and wild-type mice in all brain tissues, being hippocampus and cortex the most affected regions. Alterations in numerous metabolites were detected including phospholipids, fatty acids, purine and pyrimidine metabolites, acylcarnitines, sterols and amino acids, among others. Furthermore, metabolic pathway analysis revealed important alterations in homeostasis of lipids, energy management, and metabolism of amino acids and nucleotides. Therefore, these findings demonstrate the potential of metabolomic screening and the use of transgenic models for understanding pathogenesis of Alzheimer's disease.

Keywords: APP/PS1 mice; Alzheimer's disease; Brain regions; Direct infusion mass spectrometry; Metabolomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / genetics
Alzheimer Disease / metabolism*
Amyloid beta-Protein Precursor* / genetics
Animals
Brain / metabolism*
Disease Models, Animal*
Female
Male
Mass Spectrometry / methods
Metabolomics / methods*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Presenilin-1* / genetics

Substances

Amyloid beta-Protein Precursor
Presenilin-1
presenilin 1, mouse