Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer's disease

Metabolomic analysis of brain tissue from transgenic mouse models of Alzheimer's disease has demonstrated a great potential for the study of pathological mechanisms and the development of new therapies and biomarkers for diagnosis. However, in order to translate these investigations to the clin...

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Autores: González Domínguez, Raúl, García Barrera, Tamara, Vitorica Ferrández, Francisco Javier, Gómez Ariza, José Luis
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2015
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/139922
Acceso en línea:https://hdl.handle.net/11441/139922
https://doi.org/10.1016/j.jpba.2015.01.025
Access Level:acceso abierto
Palabra clave:MetabolomicsAPP/PS1 mice
DI-ESI-MSFI-APPI-MS
Alzheimer's disease
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spelling Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer's diseaseGonzález Domínguez, RaúlGarcía Barrera, TamaraVitorica Ferrández, Francisco JavierGómez Ariza, José LuisMetabolomicsAPP/PS1 miceDI-ESI-MSFI-APPI-MSAlzheimer's diseaseMetabolomic analysis of brain tissue from transgenic mouse models of Alzheimer's disease has demonstrated a great potential for the study of pathological mechanisms and the development of new therapies and biomarkers for diagnosis. However, in order to translate these investigations to the clinical practice it is necessary to corroborate these findings in peripheral samples. To this end, this work considers the application of a novel metabolomic platform based on the combination of a two-steps extraction procedure with complementary analysis by direct infusion electrospray mass spectrometry and flow infusion atmospheric pressure photoionization mass spectrometry for a holistic investigation of metabolic abnormalities in serum samples from APP/PS1 mice. A number of metabolites were found to be perturbed in this mouse model, including increased levels of di- and tri-acylglycerols, eicosanoids, inosine, choline and glycerophosphoethanolamine; reduced content of cholesteryl esters, free fatty acids, lysophosphocholines, amino acids, energy-related metabolites, phosphoethanolamine and urea, as well as abnormal distribution of phosphocholines depending on the fatty acid linked to the molecular moiety. This allowed the elucidation of possible pathways disturbed underlying to disease (abnormal homeostasis of phospholipids leading to membrane breakdown, energy-related failures, hyperammonemia and hyperlipidemia, among others), thus demonstrating the utility of peripheral samples to investigate pathology in the APP/PS1 model.Ministerio de Ciencia e Innovación CTM2012-38720-C03- 01 and P012-FQM-0442 and P009-FQM-4659.ElsevierBioquímica y Biología MolecularMinisterio de Ciencia e Innovación (MICIN). España2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/139922https://doi.org/10.1016/j.jpba.2015.01.025reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésJournal of Pharmaceutical and Biomedical Analysis, 107, 378-385.CTM2012-38720-C03- 01P012-FQM-0442P009-FQM-4659https://doi.org/10.1016/j.jpba.2015.01.025info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1399222026-06-17T12:51:07Z
dc.title.none.fl_str_mv Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer's disease
title Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer's disease
spellingShingle Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer's disease
González Domínguez, Raúl
MetabolomicsAPP/PS1 mice
DI-ESI-MSFI-APPI-MS
Alzheimer's disease
title_short Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer's disease
title_full Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer's disease
title_fullStr Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer's disease
title_full_unstemmed Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer's disease
title_sort Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer's disease
dc.creator.none.fl_str_mv González Domínguez, Raúl
García Barrera, Tamara
Vitorica Ferrández, Francisco Javier
Gómez Ariza, José Luis
author González Domínguez, Raúl
author_facet González Domínguez, Raúl
García Barrera, Tamara
Vitorica Ferrández, Francisco Javier
Gómez Ariza, José Luis
author_role author
author2 García Barrera, Tamara
Vitorica Ferrández, Francisco Javier
Gómez Ariza, José Luis
author2_role author
author
author
dc.contributor.none.fl_str_mv Bioquímica y Biología Molecular
Ministerio de Ciencia e Innovación (MICIN). España
dc.subject.none.fl_str_mv MetabolomicsAPP/PS1 mice
DI-ESI-MSFI-APPI-MS
Alzheimer's disease
topic MetabolomicsAPP/PS1 mice
DI-ESI-MSFI-APPI-MS
Alzheimer's disease
description Metabolomic analysis of brain tissue from transgenic mouse models of Alzheimer's disease has demonstrated a great potential for the study of pathological mechanisms and the development of new therapies and biomarkers for diagnosis. However, in order to translate these investigations to the clinical practice it is necessary to corroborate these findings in peripheral samples. To this end, this work considers the application of a novel metabolomic platform based on the combination of a two-steps extraction procedure with complementary analysis by direct infusion electrospray mass spectrometry and flow infusion atmospheric pressure photoionization mass spectrometry for a holistic investigation of metabolic abnormalities in serum samples from APP/PS1 mice. A number of metabolites were found to be perturbed in this mouse model, including increased levels of di- and tri-acylglycerols, eicosanoids, inosine, choline and glycerophosphoethanolamine; reduced content of cholesteryl esters, free fatty acids, lysophosphocholines, amino acids, energy-related metabolites, phosphoethanolamine and urea, as well as abnormal distribution of phosphocholines depending on the fatty acid linked to the molecular moiety. This allowed the elucidation of possible pathways disturbed underlying to disease (abnormal homeostasis of phospholipids leading to membrane breakdown, energy-related failures, hyperammonemia and hyperlipidemia, among others), thus demonstrating the utility of peripheral samples to investigate pathology in the APP/PS1 model.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/139922
https://doi.org/10.1016/j.jpba.2015.01.025
url https://hdl.handle.net/11441/139922
https://doi.org/10.1016/j.jpba.2015.01.025
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of Pharmaceutical and Biomedical Analysis, 107, 378-385.
CTM2012-38720-C03- 01
P012-FQM-0442
P009-FQM-4659
https://doi.org/10.1016/j.jpba.2015.01.025
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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