Background: Neurogenesis, the key mechanism to generate new neurons from existing stem cell niches continues throughout the life in the adult mammalian brain, although decelerate with aging or the progression of neurodegenerative disorders like Alzheimer’s disease (AD). In the past few years, impaired adult hippocampal neurogenesis emerged as a contributing hallmark of AD pathophysiology along with amyloid beta (Aβ) and tau hyper phosphorylation-induced neurotoxicity. However, no conclusive evidence exists that indicates the up/down-regulation of adult hippocampal neurogenesis during the course of AD progression.

Methods: In this study, we examined alterations in adult hippocampal neurogenesis and cognitive deficits using Aβ(1-42)-induced mouse model of AD.

Results: Our results demonstrate that Aβ administration induces an anxiety like behavior and impairs spatial and non-spatial memory and learning in BALB/c mice. Extensive neuronal loss was also evident in the dentate gyrus (DG), CA1, CA2 and CA3 regions of hippocampus in Aβ-treated animals. Furthermore, Aβ-exposure markedly reduced the real-time expression of markers of cell proliferation and migration i.e. Ki67 and DCX, whereas immunohistochemistry analysis revealed a substantial reduction in the expression levels of Ki67 and NeuN.

Conclusion: Our findings highlight the association of Aβ-induced neurotoxicity with altered neurogenesis and memory formation; however further insight is warranted to explore the underlying molecular pathway(s). Moreover, the treatment strategies aiming to repair the adult hippocampal neurogenesis hold potential as AD therapeutics.

背景：神经发生是从现有干细胞生态位生成新神经元的关键机制，它在成年哺乳动物大脑的整个生命周期中持续存在，但随着衰老或神经退行性疾病（如阿尔茨海默病 (AD)）的进展而减速。在过去几年中，成年海马神经发生受损与淀粉样蛋白 β (Aβ) 和 tau 过度磷酸化诱导的神经毒性一起成为 AD 病理生理学的一个重要标志。然而，没有确凿的证据表明在 AD 进展过程中成人海马神经发生的上调/下调。

方法：在这项研究中，我们使用 Aβ(1-42) 诱导的 AD 小鼠模型检查了成年海马神经发生和认知缺陷的改变。

结果：我们的结果表明，在 BALB/c 小鼠中，Aβ 给药会诱发焦虑样行为并损害空间和非空间记忆和学习。在 Aβ 治疗的动物海马的齿状回 (DG)、CA1、CA2 和 CA3 区域也明显出现广泛的神经元丢失。此外，Aβ 暴露显着降低了细胞增殖和迁移标志物（即 Ki67 和 DCX）的实时表达，而免疫组织化学分析显示 Ki67 和 NeuN 的表达水平显着降低。

结论：我们的研究结果强调了 Aβ 诱导的神经毒性与改变的神经发生和记忆形成之间的关联；然而，有必要进一步了解以探索潜在的分子途径。此外，旨在修复成年海马神经发生的治疗策略具有作为 AD 疗法的潜力。