Memantine, a non-competitive NMDA receptor antagonist possessing neuroprotective properties, belongs to the small group of drugs which have been approved for the treatment of Alzheimer's disease (AD). While several preclinical studies employing different transgenic AD mouse models have described beneficial effects with regard to rescued behavioral deficits or reduced amyloid plaque pathology, it is largely unknown whether memantine might have beneficial effects on neurodegeneration. In the current study, we assessed whether memantine treatment has an impact on hippocampal neuron loss and associated behavioral deficits in the Tg4-42 mouse model of AD. We demonstrate that a chronic oral memantine treatment for 4 months diminishes hippocampal CA1 neuron loss and rescues learning and memory performance in different behavioral paradigms, such as Morris water maze or a novel object recognition task. Cognitive benefits of chronic memantine treatment were accompanied by an amelioration of impaired adult hippocampal neurogenesis. Taken together, our results demonstrate that memantine successfully counteracts pathological alterations in a preclinical mouse model of AD.

中文翻译：

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慢性美金刚治疗可改善阿尔茨海默病模型中的行为缺陷、神经元丢失和神经发生受损。

美金刚是一种具有神经保护特性的非竞争性 NMDA 受体拮抗剂，属于已被批准用于治疗阿尔茨海默病 (AD) 的一小部分药物。虽然几项采用不同转基因 AD 小鼠模型的临床前研究已经描述了在挽救行为缺陷或减少淀粉样斑块病理方面的有益效果，但美金刚是否可能对神经退行性疾病具有有益影响在很大程度上是未知的。在当前的研究中，我们评估了美金刚治疗是否对 AD 的 Tg4-42 小鼠模型中的海马神经元丢失和相关的行为缺陷有影响。我们证明了 4 个月的长期口服美金刚治疗减少了海马 CA1 神经元的丢失，并在不同的行为范式中挽救了学习和记忆表现，例如莫里斯水迷宫或新的物体识别任务。慢性美金刚治疗的认知益处伴随着受损的成年海马神经发生的改善。总之，我们的结果表明美金刚成功地抵消了 AD 临床前小鼠模型的病理改变。