2026-05-31T22:29:34Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/119772026-02-03T11:47:04Zcom_10630_2254col_10630_37959

00925njm 22002777a 4500 dc Fernández-Valenzuela, Juan José author Sánchez-Varo, Raquel María author De Castro Carratalá, Vanessa author Moyano, Francisco author Vizuete, María Luisa author Dávila-Cansino, José Carlos author Vitorica Ferrández, Javier author Gutiérrez-Pérez, Antonia author 2016-09-09 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) http://hdl.handle.net/10630/11977 Alzheimer, Enfermedad de Hipocampo (Cerebro) Epothilone-d rescues cognition and attenuates alzheimer’s disease-like pathology in APP/PS1 mice