Department of Neurobiology and Department of Neurology of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China; Department of Physiology and Pharmacology, Medical School of Ningbo University, Ningbo, Zhejiang Province, 315211, China.
Department of Neurobiology and Department of Neurology of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310058, China; NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310058, China.
Stem Cell Reports. 2021 Jan 12;16(1):89-105. doi: 10.1016/j.stemcr.2020.12.003. Epub 2020 Dec 30.
Adult neurogenesis is impaired in the hippocampus of patients with Alzheimer disease (AD) as well as AD models. However, it is far from clear how modulating adult neurogenesis affects AD neuropathology. We confirm that adult hippocampal neurogenesis is impaired in two AD models. Surprisingly, however, cognitive functions are improved in AD models after ablating adult neural stem cells (aNSCs). Ablation of aNSCs does not affect the levels of amyloid β but restores the normal synaptic transmission in the dentate gyrus (DG) granule cells of AD models. Furthermore, calbindin depletion in the DG of AD mice is ameliorated after aNSC ablation, and knocking down calbindin abolishes the effects of aNSC ablation on synaptic and cognitive functions of AD mice. Together, our data suggest that cognitive functions of AD mice are improved after aNSC ablation, which is associated with the restoration of synaptic transmission in the DG granule cells with calbindin as an important mediator.
成人神经发生在阿尔茨海默病（AD）患者以及 AD 模型的海马体中受到损害。然而，调节成人神经发生如何影响 AD 神经病理学还远不清楚。我们证实两种 AD 模型中的成年海马神经发生受损。然而，令人惊讶的是，在去除成年神经干细胞（aNSCs）后，AD 模型的认知功能得到改善。aNSCs 的消融不会影响淀粉样蛋白 β 的水平，但会恢复 AD 模型中齿状回（DG）颗粒细胞的正常突触传递。此外，AD 小鼠 DG 中的钙结合蛋白耗竭在 aNSC 消融后得到改善，而钙结合蛋白的敲低则消除了 aNSC 消融对 AD 小鼠突触和认知功能的影响。总之，我们的数据表明，AD 小鼠的认知功能在 aNSC 消融后得到改善，这与 DG 颗粒细胞中突触传递的恢复有关，钙结合蛋白是一个重要的介质。
