Publication:
Distinct Microglial Responses in Two Transgenic Murine Models of TAU Pathology.

dc.contributor.authorRomero-Molina, Carmen
dc.contributor.authorNavarro, Victoria
dc.contributor.authorSanchez-Varo, Raquel
dc.contributor.authorJimenez, Sebastian
dc.contributor.authorFernandez-Valenzuela, Juan J
dc.contributor.authorSanchez-Mico, Maria V
dc.contributor.authorMuñoz-Castro, Clara
dc.contributor.authorGutierrez, Antonia
dc.contributor.authorVitorica, Javier
dc.contributor.authorVizuete, Marisa
dc.contributor.funderEuropean Union (EU)
dc.contributor.funderConsejeria de Economia, Innovacion, Ciencia y Empleo, Junta de Andalucia Proyecto de Excelencia
dc.date.accessioned2023-01-25T10:25:24Z
dc.date.available2023-01-25T10:25:24Z
dc.date.issued2018-11-14
dc.description.abstractMicroglial cells are crucial players in the pathological process of neurodegenerative diseases, such as Alzheimer's disease (AD). Microglial response in AD has been principally studied in relation to amyloid-beta pathology but, comparatively, little is known about inflammatory processes associated to tau pathology. In the hippocampus of AD patients, where tau pathology is more prominent than amyloid-beta pathology, a microglial degenerative process has been reported. In this work, we have directly compared the microglial response in two different transgenic tau mouse models: ThyTau22 and P301S. Surprisingly, these two models showed important differences in the microglial profile and tau pathology. Where ThyTau22 hippocampus manifested mild microglial activation, P301S mice exhibited a strong microglial response in parallel with high phospho-tau accumulation. This differential phospho-tau expression could account for the different microglial response in these two tau strains. However, soluble (S1) fractions from ThyTau22 hippocampus presented relatively high content of soluble phospho-tau (AT8-positive) and were highly toxic for microglial cells in vitro, whereas the correspondent S1 fractions from P301S mice displayed low soluble phospho-tau levels and were not toxic for microglial cells. Therefore, not only the expression levels but the aggregation of phospho-tau should differ between both models. In fact, most of tau forms in the P301S mice were aggregated and, in consequence, forming insoluble tau species. We conclude that different factors as tau mutations, accumulation, phosphorylation, and/or aggregation could account for the distinct microglial responses observed in these two tau models. For this reason, deciphering the molecular nature of toxic tau species for microglial cells might be a promising therapeutic approach in order to restore the deficient immunological protection observed in AD hippocampus.
dc.description.versionSi
dc.identifier.citationRomero-Molina C, Navarro V, Sanchez-Varo R, Jimenez S, Fernandez-Valenzuela JJ, Sanchez-Mico MV, et al. Distinct Microglial Responses in Two Transgenic Murine Models of TAU Pathology. Front Cell Neurosci. 2018 Nov 14;12:421.
dc.identifier.doi10.3389/fncel.2018.00421
dc.identifier.issn1662-5102
dc.identifier.pmcPMC6246744
dc.identifier.pmid30487735
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246744/pdf
dc.identifier.unpaywallURLhttps://www.frontiersin.org/articles/10.3389/fncel.2018.00421/pdf
dc.identifier.urihttp://hdl.handle.net/10668/13256
dc.journal.titleFrontiers in cellular neuroscience
dc.journal.titleabbreviationFront Cell Neurosci
dc.language.isoen
dc.organizationInstituto de Investigación Biomédica de Málaga-IBIMA
dc.organizationInstituto de Biomedicina de Sevilla-IBIS
dc.organizationHospital Universitario Virgen del Rocío
dc.page.number12
dc.provenanceRealizada la curación de contenido 04/04/2025
dc.publisherFrontiers Research Foundation
dc.pubmedtypeJournal Article
dc.relation.projectIDPI15/00957
dc.relation.projectIDPI15/00796
dc.relation.projectIDCTS-2035
dc.relation.publisherversionhttps://doi.org/10.3389/fncel.2018.00421
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAlzheimer disease
dc.subjectinflammation
dc.subjectmicroglia
dc.subjecttau models
dc.subjecttauopathies
dc.subject.decsPatología
dc.subject.decsRatones
dc.subject.decsHipocampo
dc.subject.decsMicroglía
dc.subject.decsAmiloide
dc.subject.decsFosforilación
dc.subject.decsEnfermedades neurodegenerativas
dc.subject.decsMutación
dc.subject.decsEnfermedad de Alzheimer
dc.subject.meshMice
dc.subject.meshAlzheimer Disease
dc.subject.meshNeurodegenerative Diseases
dc.subject.meshMicroglia
dc.subject.meshPhosphorylation
dc.subject.meshAmyloid beta-Peptides
dc.subject.meshHippocampus
dc.subject.meshMutation Accumulation
dc.titleDistinct Microglial Responses in Two Transgenic Murine Models of TAU Pathology.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number12
dspace.entity.typePublication

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