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&apos

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...

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Autores: González Domínguez, Raúl, García Barrera, Tamara, Vitorica, Javier, Gómez Ariza, José Luis
Formato: artículo
Fecha de publicación:2015
País:España
Recursos:Universidad de Huelva (UHU)
Repositorio:Arias Montano. Repositorio Institucional de la Universidad de Huelva
Idioma:inglés
OAI Identifier:oai:ariasmontano.uhu.es:10272/14596
Acesso em linha:http://hdl.handle.net/10272/14596
Access Level:acceso abierto
Palavra-chave:Metabolomics
APP/PS1 mice
DI-ESI-MS
MetaFI-APPI-MS
Alzheimer&apos
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&aposs diseaseGonzález Domínguez, RaúlGarcía Barrera, TamaraVitorica, JavierGómez Ariza, José LuisMetabolomicsAPP/PS1 miceDI-ESI-MSMetaFI-APPI-MSAlzheimer&aposs 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.Elsevier20152015-01-0120152015-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10272/14596reponame:Arias Montano. Repositorio Institucional de la Universidad de Huelvainstname:Universidad de Huelva (UHU)InglésengMinisterio de Educacion [AP2010-4278, P012-FQM-0442, P009-FQM-4659]info:eu-repo grantAgreement Ministerio de Ciencia e Innovacion [CTM2012-38720-C03-01]open accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-SinDerivadas 3.0 Españahttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:ariasmontano.uhu.es:10272/145962026-06-02T14:58:11Z
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&apos
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&apos
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&apos
González Domínguez, Raúl
Metabolomics
APP/PS1 mice
DI-ESI-MS
MetaFI-APPI-MS
Alzheimer&apos
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&apos
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&apos
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&apos
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&apos
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&apos
dc.creator.none.fl_str_mv González Domínguez, Raúl
García Barrera, Tamara
Vitorica, Javier
Gómez Ariza, José Luis
author González Domínguez, Raúl
author_facet González Domínguez, Raúl
García Barrera, Tamara
Vitorica, Javier
Gómez Ariza, José Luis
author_role author
author2 García Barrera, Tamara
Vitorica, Javier
Gómez Ariza, José Luis
author2_role author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Metabolomics
APP/PS1 mice
DI-ESI-MS
MetaFI-APPI-MS
Alzheimer&apos
s disease
topic Metabolomics
APP/PS1 mice
DI-ESI-MS
MetaFI-APPI-MS
Alzheimer&apos
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
2015-01-01
2015
2015-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10272/14596
url http://hdl.handle.net/10272/14596
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Educacion [AP2010-4278, P012-FQM-0442, P009-FQM-4659]info:eu-repo grantAgreement Ministerio de Ciencia e Innovacion [CTM2012-38720-C03-01]
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-SinDerivadas 3.0 España
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-SinDerivadas 3.0 España
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Arias Montano. Repositorio Institucional de la Universidad de Huelva
instname:Universidad de Huelva (UHU)
instname_str Universidad de Huelva (UHU)
reponame_str Arias Montano. Repositorio Institucional de la Universidad de Huelva
collection Arias Montano. Repositorio Institucional de la Universidad de Huelva
repository.name.fl_str_mv
repository.mail.fl_str_mv
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