Inflammatory Response in the Hippocampus of PS1M146L/APP751SL Mouse Model of Alzheimer's Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic

12 páginas, 5 figuras.

Detalles Bibliográficos
Autores: Jiménez-Reyes, Sebastián, Baglietto-Vargas, David, Caballero, Cristina, Moreno-González, Inés, Torres, Manuel, Sánchez-Varo, Raquel, Ruano, Diego, Vizuete, Marisa, Gutiérrez, Antonia, Vitorica, Javier
Tipo de recurso: artículo
Fecha de publicación:2008
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/38597
Acceso en línea:http://hdl.handle.net/10261/38597
Access Level:acceso abierto
Palabra clave:Alzheimer
Transgenic model
Neuroinflammation
Hippocampus Aβ plaques
Oligomers
Hippocampus
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spelling Inflammatory Response in the Hippocampus of PS1M146L/APP751SL Mouse Model of Alzheimer's Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to ClassicJiménez-Reyes, SebastiánBaglietto-Vargas, DavidCaballero, CristinaMoreno-González, InésTorres, ManuelSánchez-Varo, RaquelRuano, DiegoVizuete, MarisaGutiérrez, AntoniaVitorica, JavierAlzheimerTransgenic modelNeuroinflammationHippocampus Aβ plaquesOligomersHippocampus12 páginas, 5 figuras.Although the microglial activation is concomitant to the Alzheimer's disease, its precise role (neuroprotection vs neurodegeneration) has not yet been resolved. Here, we show the existence of an age-dependent phenotypic change of microglial activation in the hippocampus of PS1xAPP model, from an alternative activation state with Aβ phagocytic capabilities (at 6 months) to a classic cytotoxic phenotype (expressing TNF-α and related factors) at 18 months of age. This switch was coincident with high levels of soluble Aβ oligomers and a significant pyramidal neurodegeneration. In vitro assays, using astromicroglial cultures, demonstrated that oligomeric Aβ42 and soluble extracts from 18-month-old PS1xAPP hippocampus produced a potent TNF-α induction whereas monomeric Aβ42 and soluble extract from 6- or 18-month-old control and 6-month-old PS1xAPP hippocampi produced no stimulation. This stimulatory effect was avoided by immunodepletion using 6E10 or A11. In conclusion, our results show evidence of a switch in the activated microglia phenotype from alternative, at the beginning of Aβ pathology, to a classical at advanced stage of the disease in this model. This change was induced, at least in part, by the age-dependent accumulation of extracellular soluble Aβ oligomers. Finally, these cytotoxic activated microglial cells could participate in the neuronal lost observed in AD.This work was supported by Fondo de Investigación Sanitaria (FIS) from Instituto de Salud Carlos III of Spain through Grants PI060567 (J.V.), PI060556 (A.G.), and PI060781 (D.R.), and by Junta de Andalucia, Proyecto de Excelencia CVI-902. S.J. and I.M.-G. are the recipients of a contract from CIBERNED. D.B.-V. and M.T. were recipients of PhD fellowships from Junta de Andalucia and R.S.-V. and C.C. from Ministerio de Educación y Ciencia (MEC) of Spain.Peer reviewedSociety for Neuroscience201120112008info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/38597reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1523/​JNEUROSCI.3024-08.2008info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/385972026-05-22T06:33:51Z
dc.title.none.fl_str_mv Inflammatory Response in the Hippocampus of PS1M146L/APP751SL Mouse Model of Alzheimer's Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic
title Inflammatory Response in the Hippocampus of PS1M146L/APP751SL Mouse Model of Alzheimer's Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic
spellingShingle Inflammatory Response in the Hippocampus of PS1M146L/APP751SL Mouse Model of Alzheimer's Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic
Jiménez-Reyes, Sebastián
Alzheimer
Transgenic model
Neuroinflammation
Hippocampus Aβ plaques
Oligomers
Hippocampus
title_short Inflammatory Response in the Hippocampus of PS1M146L/APP751SL Mouse Model of Alzheimer's Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic
title_full Inflammatory Response in the Hippocampus of PS1M146L/APP751SL Mouse Model of Alzheimer's Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic
title_fullStr Inflammatory Response in the Hippocampus of PS1M146L/APP751SL Mouse Model of Alzheimer's Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic
title_full_unstemmed Inflammatory Response in the Hippocampus of PS1M146L/APP751SL Mouse Model of Alzheimer's Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic
title_sort Inflammatory Response in the Hippocampus of PS1M146L/APP751SL Mouse Model of Alzheimer's Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic
dc.creator.none.fl_str_mv Jiménez-Reyes, Sebastián
Baglietto-Vargas, David
Caballero, Cristina
Moreno-González, Inés
Torres, Manuel
Sánchez-Varo, Raquel
Ruano, Diego
Vizuete, Marisa
Gutiérrez, Antonia
Vitorica, Javier
author Jiménez-Reyes, Sebastián
author_facet Jiménez-Reyes, Sebastián
Baglietto-Vargas, David
Caballero, Cristina
Moreno-González, Inés
Torres, Manuel
Sánchez-Varo, Raquel
Ruano, Diego
Vizuete, Marisa
Gutiérrez, Antonia
Vitorica, Javier
author_role author
author2 Baglietto-Vargas, David
Caballero, Cristina
Moreno-González, Inés
Torres, Manuel
Sánchez-Varo, Raquel
Ruano, Diego
Vizuete, Marisa
Gutiérrez, Antonia
Vitorica, Javier
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer
Transgenic model
Neuroinflammation
Hippocampus Aβ plaques
Oligomers
Hippocampus
topic Alzheimer
Transgenic model
Neuroinflammation
Hippocampus Aβ plaques
Oligomers
Hippocampus
description 12 páginas, 5 figuras.
publishDate 2008
dc.date.none.fl_str_mv 2008
2011
2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/38597
url http://hdl.handle.net/10261/38597
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1523/​JNEUROSCI.3024-08.2008
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869416199464419328
score 15,81155

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