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dc.contributor.authorAlmoda, Beatriz
dc.contributor.authorLabra, Carmen de
dc.contributor.authorBarrera, Iliana
dc.contributor.authorGruart, Agnés
dc.contributor.authorDelgado-García, José M.
dc.contributor.authorVillacampa, Nàdia
dc.contributor.authorVilella, Antonietta
dc.contributor.authorHofer, Markus J.
dc.contributor.authorHidalgo, Juan
dc.contributor.authorCampbell, Iain L.
dc.contributor.authorGonzález, Berta
dc.contributor.authorCastellano, Bernardo
dc.date.accessioned2024-01-16T09:09:12Z
dc.date.issued2015-03
dc.identifier.citationAlmolda B, de Labra C, Barrera I, Gruart A, Delgado-Garcia JM, Villacampa N, Vilella A, Hofer MJ, Hidalgo J, Campbell IL, González B, Castellano B. Alterations in microglial phenotype and hippocampal neuronal function in transgenic mice with astrocyte-targeted production of interleukin-10. Brain Behav Immun. 2015 Mar;45:80-97.es_ES
dc.identifier.issn0889-1591
dc.identifier.urihttp://hdl.handle.net/2183/34917
dc.description.abstract[Abstract] Interleukin-10 (IL-10) is a cytokine classically linked with anti-inflammatory and protective functions in the central nervous system (CNS) in different neurodegenerative and neuroinflammatory conditions. In order to study the specific role of local CNS produced IL-10, we have created a new transgenic mouse line with astrocyte-targeted production of IL-10 (GFAP-IL10Tg). In the present study, the effects of local CNS IL-10 production on microglia, astrocytes and neuronal connectivity under basal conditions were investigated using immunohistochemistry, molecular biology techniques, electrophysiology and behavioural studies. Our results showed that, in GFAP-IL10Tg animals, microglia displayed an increase in density and a specific activated phenotype characterised by morphological changes in specific areas of the brain including the hippocampus, cortex and cerebellum that correlated with the level of transgene expressed IL-10 mRNA. Distinctively, in the hippocampus, microglial cells adopted an elongated morphology following the same direction as the dendrites of pyramidal neurons. Moreover, this IL-10-induced microglial phenotype showed increased expression of certain molecules including Iba1, CD11b, CD16/32 and F4/80 markers, "de novo" expression of CD150 and no detectable levels of either CD206 or MHCII. To evaluate whether this specific activated microglial phenotype was associated with changes in neuronal activity, the electrophysiological properties of pyramidal neurons of the hippocampus (CA3-CA1) were analysed in vivo. We found a lower excitability of the CA3-CA1 synapses and absence of long-term potentiation (LTP) in GFAP-IL10Tg mice. This study is the first description of a transgenic mouse with astrocyte-targeted production of the cytokine IL-10. The findings indicate that IL-10 induces a specific activated microglial phenotype concomitant with changes in hippocampal LTP responses. This transgenic animal will be a very useful tool to study IL-10 functions in the CNS, not only under basal conditions, but also after different experimental lesions or induced diseases.es_ES
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relation.urihttps://doi.org/10.1016/j.bbi.2014.10.015es_ES
dc.subjectCD11bes_ES
dc.subjectCD150es_ES
dc.subjectCD16/32es_ES
dc.subjectCytokinees_ES
dc.subjectF4/80es_ES
dc.subjectGFAPes_ES
dc.subjectGliosises_ES
dc.subjectIL-10Res_ES
dc.subjectIba1es_ES
dc.subjectLTPes_ES
dc.subjectMicroglial plasticityes_ES
dc.subjectNeuroinflammationes_ES
dc.subjectTransgenic micees_ES
dc.titleAlterations in microglial phenotype and hippocampal neuronal function in transgenic mice with astrocyte-targeted production of interleukin-10es_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessinfo:eu-repo/semantics/embargoedAccesses_ES
dc.date.embargoEndDate9999-99-99es_ES
dc.date.embargoLift9999-99-99
UDC.journalTitleBrain, Behavior, and Immunityes_ES
UDC.volume45es_ES
UDC.startPage80es_ES
UDC.endPage97es_ES


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