BACKGROUND Studies have suggested that cognitive impairment in Alzheimer's disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. OBJECTIVE In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. RESULTS It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. CONCLUSION These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.

中文翻译：

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氟西汀可预防中年APPswe / PSEN1dE9双转基因阿尔茨海默氏病小鼠的树突棘丢失。

背景研究表明，阿尔茨海默氏病（AD）的认知障碍与树突棘丧失有关，尤其是在海马中。氟西汀（FLX）已被证明可以改善AD的早期认知，并与减少海马突触变性有关。然而，关于FLX是否在中晚期阶段影响AD的发病机制以及其作用与海马树突功能障碍的改善是否相关还鲜为人知。以前，已经观察到FLX可以改善中年APP / PS1小鼠的空间学习能力。目的在本研究中，我们进一步表征了FLX对中年APP / PS1小鼠海马树突棘的影响。结果发现齿状回（DG）中的树突棘数量，FLX显着增加海马CA1和CA2 / 3。同时，FLX有效减弱了Ser396上tau的过度磷酸化，并提高了海马突触后密度95（PSD-95）和突触蛋白1（SYN-1）的蛋白水平。结论这些结果表明，在FLX治疗的中年APP / PS1小鼠中观察到的增强的学习能力可能与FLX显着缓解海马树突状脊柱病理有关，并暗示FLX有望被探索为AD治疗AD的新策略。中后期。