荷兰神经科学研究所Evgenia Salta、比利时鲁汶大学Bart De Strooper等研究人员合作发现，恢复miR-132的表达可挽救成年海马神经发生和阿尔茨海默氏病的记忆缺陷。这一研究成果于2021年5月24日在线发表在国际学术期刊《细胞—干细胞》上。

研究人员表示，驻留在海马神经源性微环境中的神经干细胞在成年大脑中维持终生的神经发生。成人海马神经发生（AHN）在功能上与人类和啮齿动物的记忆和认知可塑性有关。在阿尔茨海默氏病（AD）中，在海马神经源性微环境中产生新神经元的过程受到阻碍，但其机制尚不清楚。

研究人员发现，miR-132是AD中最一致性下调的microRNA之一，并且是AHN的有效调节因子，在成体神经干细胞及其后代中发挥细胞自主的促神经源性作用。使用不同的AD小鼠模型、培养的人类原代和建立的神经干细胞以及人类患者的材料，研究人员证明AHN直接受到AD病理学的影响。成年小鼠AD海马中的miR-132替代可恢复AHN和相关的记忆缺陷。这些发现证实了AHN在AD小鼠模型中的重要性，并揭示了在神经退行性病变中靶向miR-132的潜在治疗潜力。

 附：英文原文

Title: Restoring miR-132 expression rescues adult hippocampal neurogenesis and memory deficits in Alzheimer’s disease

Author: Hannah Walgrave, Sriram Balusu, Sarah Snoeck, Elke Vanden Eynden, Katleen Craessaerts, Nicky Thrupp, Leen Wolfs, Katrien Horré, Yannick Fourne, Alicja Ronisz, Edina Silajdi, Amber Penning, Giorgia Tosoni, Zsuzsanna Callaerts-Vegh, Rudi D’Hooge, Dietmar Rudolf Thal, Henrik Zetterberg, Sandrine Thuret, Mark Fiers, Carlo Sala Frigerio, Bart De Strooper, Evgenia Salta

Issue&Volume: 2021-05-24

Abstract: Neural stem cells residing in the hippocampal neurogenic niche sustain lifelong neurogenesis in the adult brain. Adult hippocampal neurogenesis (AHN) is functionally linked to mnemonic and cognitive plasticity in humans and rodents. In Alzheimer’s disease (AD), the process of generating new neurons at the hippocampal neurogenic niche is impeded, yet the mechanisms involved are unknown. Here we identify miR-132, one of the most consistently downregulated microRNAs in AD, as a potent regulator of AHN, exerting cell-autonomous proneurogenic effects in adult neural stem cells and their progeny. Using distinct AD mouse models, cultured human primary and established neural stem cells, and human patient material, we demonstrate that AHN is directly affected by AD pathology. miR-132 replacement in adult mouse AD hippocampus restores AHN and relevant memory deficits. Our findings corroborate the significance of AHN in mouse models of AD and reveal the possible therapeutic potential of targeting miR-132 in neurodegeneration.

DOI: 10.1016/j.stem.2021.05.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00219-8