Alzheimer's disease (AD) is a neurodegenerative disorder with notable factors of dysfunction in multiple neurological changes, encompassing neuronal loss in the frontal cortex and hippocampal regions. Dysfunction of proliferation and self-renewal of neural stem cells (NSCs) was observed in AD patients and animals. Thereby, mobilizing endogenous neurogenesis by pharmacological agents would provide a promising route for neurodegeneration. Osthole (Ost), a natural coumarin derivative, has been reported to exert extensive neuroprotective effects in AD. However, whether ost can facilitate endogenous neurogenesis against AD in vivo is still unknown. In this study, by using Morris water maze (MWM) test, hematoxylin-eosin (HE) staining, Nissl staining, immunofluorescence analysis and western blot, we demonstrated that oral administration of ost could improve the learning and memory function, inhibit neuronal apoptosis, elevate the expression of glial cell line derived neurotrophic factor (GDNF), synaptophysin (SYP) and postsynaptic density protein 95 (PSD95). Moreover, ost could remarkably enhance proliferation of NSCs and increase the amount of mature neurons in APP/PS1 transgenic mice. Together, our findings demonstrated that ost possessed the ability of promoting endogenous neurogenesis and ost could be served as a plausible agent to reverse or slow down the progress of AD.

中文翻译：

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Osthole 通过增加 APP / PS1 转基因小鼠的神经元群改善认知障碍

阿尔茨海默病 (AD) 是一种神经退行性疾病，在多个神经系统变化中具有显着的功能障碍因素，包括额叶皮层和海马区的神经元丢失。在 AD 患者和动物中观察到神经干细胞 (NSC) 的增殖和自我更新功能障碍。因此，通过药剂动员内源性神经发生将为神经变性提供一条有希望的途径。Osthole (Ost) 是一种天然香豆素衍生物，据报道在 AD 中发挥广泛的神经保护作用。然而，ost 是否可以促进体内针对 AD 的内源性神经发生仍然未知。本研究通过Morris水迷宫（MWM）试验、苏木精-伊红（HE）染色、Nissl染色、免疫荧光分析和蛋白质印迹，我们证明口服ost可以改善学习和记忆功能，抑制神经元凋亡，提高胶质细胞系衍生神经营养因子（GDNF）、突触素（SYP）和突触后密度蛋白95（PSD95）的表达。此外，ost 可显着增强 NSCs 的增殖并增加 APP/PS1 转基因小鼠的成熟神经元数量。总之，我们的研究结果表明 ost 具有促进内源性神经发生的能力，并且 ost 可以作为一种合理的药物来逆转或减缓 AD 的进展。ost 可显着增强 NSCs 的增殖并增加 APP/PS1 转基因小鼠的成熟神经元数量。总之，我们的研究结果表明 ost 具有促进内源性神经发生的能力，并且 ost 可以作为一种合理的药物来逆转或减缓 AD 的进展。ost 可显着增强 APP/PS1 转基因小鼠中神经干细胞的增殖并增加成熟神经元的数量。总之，我们的研究结果表明 ost 具有促进内源性神经发生的能力，并且 ost 可以作为一种合理的药物来逆转或减缓 AD 的进展。