Metabolomic screening of regional brain alterations in the APP/PS1 transgenic model of Alzheimer&apos

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 mode...

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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:10272/14594
Acesso em linha:http://hdl.handle.net/10272/14594
Access Level:acceso abierto
Palavra-chave:Metabolomics
APP/PS1 mice
Brain regions
Direct infusion mass spectrometry
Alzheimer&apos
s disease
Descrição
Resumo: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.