Memantine, a low- to moderate-affinity uncompetitive N-methyl-D-aspartate receptor antagonist, has been shown to improve cognitive functions in animal models of Alzheimer’s disease (AD). Here we treated APP/PS1 AD mice with a therapeutic dose of memantine (20 mg/kg/day) and examined its underlying mechanisms in ameliorating cognitive defects. Using behavioral, electrophysiological, optogenetic and morphology approaches to explore how memantine delay the pathogenesis of AD. Memantine significantly improved the acquisition in Morris water maze (MWM) in APP/PS1 mice without affecting the speed of swimming. Furthermore, memantine enhanced EC to CA1 synaptic neurotransmission and promoted dendritic spine regeneration of EC neurons that projected to CA1. Our study reveals the underlying mechanism of memantine in the treatment of AD mice.

中文翻译：

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美金刚通过增强内嗅-CA1投射改善AD小鼠的认知缺陷

美金刚是一种低到中等亲和力的非竞争性 N-甲基-D-天冬氨酸受体拮抗剂，已被证明可以改善阿尔茨海默病 (AD) 动物模型的认知功能。在这里，我们用治疗剂量的美金刚（20 mg/kg/天）治疗了 APP/PS1 AD 小鼠，并检查了其改善认知缺陷的潜在机制。使用行为学、电生理学、光遗传学和形态学方法来探索美金刚如何延缓 AD 的发病机制。美金刚在不影响游泳速度的情况下显着改善了 APP/PS1 小鼠在莫里斯水迷宫 (MWM) 中的采集。此外，美金刚增强了 EC 到 CA1 的突触神经传递，并促进了投射到 CA1 的 EC 神经元的树突棘再生。我们的研究揭示了美金刚治疗AD小鼠的潜在机制。