Metabolomic research on the role of interleukin-4 in Alzheimer’s disease

Inflammation plays a prominent role in the pathogenesis of Alzheimer’s disease, affecting both brain and the peripheral system. Thus, modulation of inflammation in animal models of this neurodegenerative disorder may be of great interest to elucidate the pathological mechanisms underlying this infla...

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Detalhes bibliográficos
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:10272/14675
Acesso em linha:http://hdl.handle.net/10272/14675
Access Level:acceso abierto
Palavra-chave:Metabolomics
APP/PS1 mice
Interleukin-4
Direct infusion mass spectrometry
Alzheimer’s disease
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spelling Metabolomic research on the role of interleukin-4 in Alzheimer’s diseaseGonzález Domínguez, RaúlGarcía Barrera, TamaraVitorica, JavierGómez Ariza, José LuisMetabolomicsAPP/PS1 miceInterleukin-4Direct infusion mass spectrometryAlzheimer’s diseaseInflammation plays a prominent role in the pathogenesis of Alzheimer’s disease, affecting both brain and the peripheral system. Thus, modulation of inflammation in animal models of this neurodegenerative disorder may be of great interest to elucidate the pathological mechanisms underlying this inflammatory component. To this end, a metabolomic investigation on a triple transgenic mouse model obtained by crossing the APP/PS1 mice with interleukin-4 knockout mice (a model of impaired immune function) was performed for the first time. Serum samples from transgenic mice and wild type animals were analyzed by direct infusion mass spectrometry followed by multivariate statistics in order to identify altered metabolites. Subsequently, metabolic pathway analysis allowed the elucidation of potential pathological mechanisms associated with the development of Alzheimer-type disorders in response to interleukin-4 deficiency, such as impaired homeostasis of histamine, altered metabolism of amino acids (threonine, aspartate and tyrosine), deregulated urea cycle and increased production of eicosanoids. Therefore, this work demonstrates the potential of this triple transgenic model with modulated immunity for the study of pathological mechanisms associated with inflammation in Alzheimer’s disease.Springer Verlag20152015-01-0120152015-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10272/14675reponame:Arias Montano. Repositorio Institucional de la Universidad de Huelvainstname:Universidad de Huelva (UHU)InglésengConsejeria de Innovacion, Ciencia y Empresa (Junta de Andalucia) [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:10272/146752026-06-02T14:58:11Z
dc.title.none.fl_str_mv Metabolomic research on the role of interleukin-4 in Alzheimer’s disease
title Metabolomic research on the role of interleukin-4 in Alzheimer’s disease
spellingShingle Metabolomic research on the role of interleukin-4 in Alzheimer’s disease
González Domínguez, Raúl
Metabolomics
APP/PS1 mice
Interleukin-4
Direct infusion mass spectrometry
Alzheimer’s disease
title_short Metabolomic research on the role of interleukin-4 in Alzheimer’s disease
title_full Metabolomic research on the role of interleukin-4 in Alzheimer’s disease
title_fullStr Metabolomic research on the role of interleukin-4 in Alzheimer’s disease
title_full_unstemmed Metabolomic research on the role of interleukin-4 in Alzheimer’s disease
title_sort Metabolomic research on the role of interleukin-4 in Alzheimer’s disease
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
Interleukin-4
Direct infusion mass spectrometry
Alzheimer’s disease
topic Metabolomics
APP/PS1 mice
Interleukin-4
Direct infusion mass spectrometry
Alzheimer’s disease
description Inflammation plays a prominent role in the pathogenesis of Alzheimer’s disease, affecting both brain and the peripheral system. Thus, modulation of inflammation in animal models of this neurodegenerative disorder may be of great interest to elucidate the pathological mechanisms underlying this inflammatory component. To this end, a metabolomic investigation on a triple transgenic mouse model obtained by crossing the APP/PS1 mice with interleukin-4 knockout mice (a model of impaired immune function) was performed for the first time. Serum samples from transgenic mice and wild type animals were analyzed by direct infusion mass spectrometry followed by multivariate statistics in order to identify altered metabolites. Subsequently, metabolic pathway analysis allowed the elucidation of potential pathological mechanisms associated with the development of Alzheimer-type disorders in response to interleukin-4 deficiency, such as impaired homeostasis of histamine, altered metabolism of amino acids (threonine, aspartate and tyrosine), deregulated urea cycle and increased production of eicosanoids. Therefore, this work demonstrates the potential of this triple transgenic model with modulated immunity for the study of pathological mechanisms associated with inflammation in Alzheimer’s disease.
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/10272/14675
url http://hdl.handle.net/10272/14675
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Consejeria de Innovacion, Ciencia y Empresa (Junta de Andalucia) [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 Springer Verlag
publisher.none.fl_str_mv Springer Verlag
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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