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Epothilone-d rescues cognition and attenuates alzheimer’s disease-like pathology in APP/PS1 mice
dc.contributor.author | Fernández-Valenzuela, Juan José | |
dc.contributor.author | Sánchez-Varo, Raquel María | |
dc.contributor.author | De Castro Carratalá, Vanessa | |
dc.contributor.author | Moyano, Francisco | |
dc.contributor.author | Vizuete, María Luisa | |
dc.contributor.author | Dávila-Cansino, José Carlos | |
dc.contributor.author | Vitorica Ferrández, Javier | |
dc.contributor.author | Gutiérrez-Pérez, Antonia | |
dc.date.accessioned | 2016-09-09T12:26:41Z | |
dc.date.available | 2016-09-09T12:26:41Z | |
dc.date.created | 2016 | |
dc.date.issued | 2016-09-09 | |
dc.identifier.uri | http://hdl.handle.net/10630/11977 | |
dc.description.abstract | AIMS: 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.sponsorship | Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. | es_ES |
dc.language.iso | eng | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | Alzheimer, Enfermedad de | es_ES |
dc.subject | Hipocampo (Cerebro) | es_ES |
dc.subject.other | Alzheimer | es_ES |
dc.subject.other | Modelo transgénico | es_ES |
dc.subject.other | Tau | es_ES |
dc.subject.other | patología | es_ES |
dc.subject.other | estabilizador microtubulos | es_ES |
dc.title | Epothilone-d rescues cognition and attenuates alzheimer’s disease-like pathology in APP/PS1 mice | es_ES |
dc.type | info:eu-repo/semantics/conferenceObject | es_ES |
dc.centro | Facultad de Ciencias | es_ES |
dc.relation.eventtitle | 10 FENS Forum of Neuroscience | es_ES |
dc.relation.eventplace | Copenhagen, Dinamarca | es_ES |
dc.relation.eventdate | 2 Julio 2016 | es_ES |
dc.rights.cc | by-nc-nd |