Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, National Stem Cell Translational Resource Center, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Aging Cell. 2023 Apr;22(4):e13794. doi: 10.1111/acel.13794. Epub 2023 Feb 16.
Hippocampal neural stem cell (NSC) proliferation is known to decline with age, which is closely linked to learning and memory impairments. In the current study, we found that the expression level of miR-181a-5p was decreased in the hippocampal NSCs of aged mice and that exogenous overexpression of miR-181a-5p promoted NSC proliferation without affecting NSC differentiation into neurons and astrocytes. The mechanistic study revealed that phosphatase and tensin homolog (PTEN), a negative regulator of the AKT signaling pathway, was the target of miR-181a-5p and knockdown of PTEN could rescue the impairment of NSC proliferation caused by low miR-181a-5p levels. Moreover, overexpression of miR-181a-5p in the dentate gyrus enhanced the proliferation of NSCs and ameliorated learning and memory impairments in aged mice. Taken together, our findings indicated that miR-181a-5p played a functional role in NSC proliferation and aging-related, hippocampus-dependent learning and memory impairments.
海马神经干细胞（NSC）的增殖已知随年龄的增长而下降，这与学习和记忆障碍密切相关。在本研究中，我们发现衰老小鼠海马 NSC 中 miR-181a-5p 的表达水平降低，外源性过表达 miR-181a-5p 可促进 NSC 增殖，而不影响 NSC 分化为神经元和星形胶质细胞。机制研究表明，磷酸酶和张力蛋白同源物（PTEN）是 AKT 信号通路的负调节剂，是 miR-181a-5p 的靶标，敲低 PTEN 可以挽救低 miR-181a-5p 水平引起的 NSC 增殖损伤。此外，在齿状回中过表达 miR-181a-5p 可增强 NSCs 的增殖，并改善衰老小鼠的学习和记忆障碍。综上所述，我们的研究结果表明，miR-181a-5p 在 NSC 增殖和与衰老相关的、海马依赖性的学习和记忆障碍中发挥功能作用。
