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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

 

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dc.creator Jiménez, Sebastián es
dc.creator Baglietto-Vargas, David es
dc.creator Caballero, Cristina M. es
dc.creator Moreno González, Inés es
dc.creator Vitorica Ferrández, Francisco Javier es
dc.date.accessioned 2016-12-12T14:15:01Z
dc.date.available 2016-12-12T14:15:01Z
dc.date.issued 2008
dc.identifier.citation Jiménez, S., Baglietto-Vargas, D., Caballero, C.M., Moreno González, I. y 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
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
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