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...
| Autores: | , , , |
|---|---|
| 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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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 |
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Arias Montano. Repositorio Institucional de la Universidad de Huelva |
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15,812429 |