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dc.contributor.authorFernández-Valenzuela, Juan José
dc.contributor.authorSánchez-Varo, Raquel María 
dc.contributor.authorDe Castro Carratalá, Vanessa
dc.contributor.authorMoyano, Francisco
dc.contributor.authorVizuete, María Luisa
dc.contributor.authorDávila-Cansino, José Carlos
dc.contributor.authorVitorica Ferrández, Javier
dc.contributor.authorGutiérrez-Pérez, Antonia 
dc.date.accessioned2016-09-09T12:26:41Z
dc.date.available2016-09-09T12:26:41Z
dc.date.created2016
dc.date.issued2016-09-09
dc.identifier.urihttp://hdl.handle.net/10630/11977
dc.description.abstractAIMS: Cognitive decline in Alzheimer's disease (AD) patients has been linked to synaptic damage and neuronal loss. Hyperphosphorylation of tau protein destabilizes microtubules leading to the accumulation of autophagy/vesicular material and the generation of dystrophic neurites, thus contributing to axonal/synaptic dysfunction. In this study, we analyzed the effect of a microtubule-stabilizing compound in the progression of the disease in the hippocampus of APP751SL/PS1M146L transgenic model. METHODS: APP/PS1 mice (3 month-old) were treated with a weekly intraperitoneal injection of 2 mg/kg epothilone-D (Epo-D) for 3 months. Vehicle-injected animals were used as controls. Mice were tested on the Morris water maze, Y-maze and object-recognition tasks for memory performance. Abeta, AT8, ubiquitin and synaptic markers levels were analyzed by Western-blots. Hippocampal plaque, synaptic and dystrophic loadings were quantified by image analysis after immunohistochemical stainings. RESULTS: Epo-D treated mice exhibited a significant improvement in the memory tests compared to controls. The rescue of cognitive deficits was associated to a significant reduction in the AD-like hippocampal pathology. Levels of Abeta, APP and ubiquitin were significantly reduced in treated animals. This was paralleled by a decrease in the amyloid burden, and more importantly, in the plaque-associated axonal dystrophy pathology. Finally, synaptic levels were significantly restored in treated animals compared to controls. CONCLUSION: Epo-D treatment promotes synaptic and spatial memory recovery, reduces the accumulation of extracellular Abeta and the associated neuritic pathology in the hippocampus of APP/PS1 model. Therefore, microtubule stabilizing drugs could be considered therapeutical candidates to slow down AD progression. Supported by FIS-PI12/01431 and PI15/00796 (AG),FIS-PI12/01439 and PI15/00957(JV)es_ES
dc.description.sponsorshipUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.es_ES
dc.language.isoenges_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectAlzheimer, Enfermedad dees_ES
dc.subjectHipocampo (Cerebro)es_ES
dc.subject.otherAlzheimeres_ES
dc.subject.otherModelo transgénicoes_ES
dc.subject.otherTaues_ES
dc.subject.otherpatologíaes_ES
dc.subject.otherestabilizador microtubuloses_ES
dc.titleEpothilone-d rescues cognition and attenuates alzheimer’s disease-like pathology in APP/PS1 micees_ES
dc.typeinfo:eu-repo/semantics/conferenceObjectes_ES
dc.centroFacultad de Cienciases_ES
dc.relation.eventtitle10 FENS Forum of Neurosciencees_ES
dc.relation.eventplaceCopenhagen, Dinamarcaes_ES
dc.relation.eventdate2 Julio 2016es_ES
dc.rights.ccby-nc-nd


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