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    •   RIUMA Principal
    • Investigación
    • Biología Celular, Genética y Fisiología - (BCGF)
    • BCGF - Contribuciones a congresos científicos
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    •   RIUMA Principal
    • Investigación
    • Biología Celular, Genética y Fisiología - (BCGF)
    • BCGF - Contribuciones a congresos científicos
    • Ver ítem

    Epothilone-d rescues cognition and attenuates alzheimer’s disease-like pathology in APP/PS1 mice

    • Autor
      Ferbandez-Valenzuela, Juan Jose; Sanchez-Varo, Raquel; De Castro, Vanessa; Moyano, Francisco; Vizuete, Marisa; Davila, Jose CarlosAutoridad Universidad de Málaga; Vitorica, Javier; Gutierrez-Perez, AntoniaAutoridad Universidad de Málaga
    • Fecha
      2016-09-09
    • Palabras clave
      Alzheimer, Enfermedad de; Hipocampo (Cerebro)
    • Resumen
      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)
    • URI
      http://hdl.handle.net/10630/11977
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    Ficheros
    FENS 2016_Certificado y Abstract Juan Jose Fernandez.pdf (2.151Mb)
    Colecciones
    • BCGF - Contribuciones a congresos científicos

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    REPOSITORIO INSTITUCIONAL UNIVERSIDAD DE MÁLAGA
    REPOSITORIO INSTITUCIONAL UNIVERSIDAD DE MÁLAGA