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dc.creatorJiménez Muñoz, Sebastiánes
dc.creatorBaglietto Vargas, Davides
dc.creatorCaballero, Cristina M.es
dc.creatorMoreno González, Inéses
dc.creatorTorres Canalejo, Manuel
dc.creatorSánchez Varo, Raquel María
dc.creatorRuano Caballero, Diego
dc.creatorVizuete Chacón, María Luisa
dc.creatorGutiérrez Pérez, Antonia
dc.creatorVitorica Ferrández, Francisco Javier
dc.date.accessioned2016-12-12T14:15:01Z
dc.date.available2016-12-12T14:15:01Z
dc.date.issued2008
dc.identifier.citationJiménez Muñoz, S., Baglietto Vargas, D., Caballero, C.M., Moreno González, I., Torres Canalejo, M., Sánchez Varo, R.M.,...,Vitorica Ferrández, F.J. (2008). Inflammatory response in the hippocampus of PS1M146L/APP 751SL mouse model of Alzheimer's disease: Age-dependent switch in the microglial phenotype from alternative to classic. Journal of Neuroscience, 28 (45), 11650-11661.
dc.identifier.issn0270-6474es
dc.identifier.urihttp://hdl.handle.net/11441/50003
dc.description.abstractAlthough 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 ADes
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherSociety for Neurosciencees
dc.relation.ispartofJournal of Neuroscience, 28 (45), 11650-11661.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAlzheimeres
dc.subjectHippocampuses
dc.subjectHippocampus Aβ plaqueses
dc.subjectNeuroinflammationes
dc.subjectOligomerses
dc.subjectTransgenic modeles
dc.titleInflammatory response in the hippocampus of PS1M146L/APP 751SL mouse model of Alzheimer's disease: Age-dependent switch in the microglial phenotype from alternative to classices
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessrightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Bioquímica y Biología Moleculares
dc.relation.publisherversion10.1523/JNEUROSCI.3024-08.2008es
idus.format.extent12 p.es
dc.journaltitleJournal of Neurosciencees
dc.publication.volumen28es
dc.publication.issue45es
dc.publication.initialPage11650es
dc.publication.endPage11661es
dc.identifier.idushttps://idus.us.es/xmlui/handle/11441/50003

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