dc.creator | Jiménez Muñoz, Sebastián | es |
dc.creator | Baglietto Vargas, David | es |
dc.creator | Caballero, Cristina M. | es |
dc.creator | Moreno González, Inés | es |
dc.creator | Torres Canalejo, Manuel | |
dc.creator | Sánchez Varo, Raquel María | |
dc.creator | Ruano Caballero, Diego | |
dc.creator | Vizuete Chacón, María Luisa | |
dc.creator | Gutiérrez Pérez, Antonia | |
dc.creator | Vitorica Ferrández, Francisco Javier | |
dc.date.accessioned | 2016-12-12T14:15:01Z | |
dc.date.available | 2016-12-12T14:15:01Z | |
dc.date.issued | 2008 | |
dc.identifier.citation | Jiménez 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.issn | 0270-6474 | es |
dc.identifier.uri | http://hdl.handle.net/11441/50003 | |
dc.description.abstract | 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 | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Society for Neuroscience | es |
dc.relation.ispartof | Journal of Neuroscience, 28 (45), 11650-11661. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Alzheimer | es |
dc.subject | Hippocampus | es |
dc.subject | Hippocampus Aβ plaques | es |
dc.subject | Neuroinflammation | es |
dc.subject | Oligomers | es |
dc.subject | Transgenic model | es |
dc.title | 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 | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular | es |
dc.relation.publisherversion | 10.1523/JNEUROSCI.3024-08.2008 | es |
idus.format.extent | 12 p. | es |
dc.journaltitle | Journal of Neuroscience | es |
dc.publication.volumen | 28 | es |
dc.publication.issue | 45 | es |
dc.publication.initialPage | 11650 | es |
dc.publication.endPage | 11661 | es |
dc.identifier.idus | https://idus.us.es/xmlui/handle/11441/50003 | |