Ablating Adult Neural Stem Cells Improves Synaptic and Cognitive Functions in Alzheimer Models.
Ablating Adult Neural Stem Cells Improves Synaptic and Cognitive Functions in Alzheimer Models.
复制标题
消除成体神经干细胞可改善阿尔茨海默病模型的突触和认知功能
DOI：
10.1016/j.stemcr.2020.12.003
复制
发表时间：
2021-01-12
影响因子：
5.9
通讯作者：
Sun B
中科院分区：
文献类型：
--
作者：
Zhang X;Mei Y;He Y;Wang D;Wang J;Wei X;Yang E;Zhou D;Shen H;Peng G;Shu Q;Li X;Luo B;Zhou Y;Sun B
阿尔茨海默病（AD）患者和AD模型的海马成体神经发生受损。然而，调节成人神经发生如何影响阿尔茨海默病的神经病理尚不清楚。我们证实，在两种AD模型中，成人海马神经发生受损。然而，令人惊讶的是，在切除成体神经干细胞（aNSCs）后，AD模型的认知功能得到改善。消融aNSCs不影响β淀粉样蛋白水平，但恢复AD模型齿状回（DG）颗粒细胞的正常突触传递。此外，aNSC消融后，AD小鼠DG中calbindin的缺失得到改善，敲除calbindin可消除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，这与以calbindin为重要介质的DG颗粒细胞突触传递的恢复有关。两种AD模型的成年海马神经发生受损，消融aNSCs后AD模型的认知功能得到改善，消融aNSCs恢复AD模型DG颗粒细胞的正常突触传递，calbindin表达改变介导了消融aNSCs对AD小鼠突触和认知功能的影响。Sun和他的同事发现，切除成体神经干细胞（aNSCs）可以改善阿尔茨海默病（AD）小鼠模型的认知功能。这种作用与齿状颗粒细胞突触传递的恢复有关。此外，calbindin的改变是AD小鼠aNSC消融和突触和认知功能改善之间的重要中介。
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. Adult hippocampal neurogenesis was impaired in two AD models Cognitive functions were improved in AD models after ablation of aNSCs Ablating aNSCs restored the normal synaptic transmission in the DG granule cells of AD models Altered expression of calbindin mediated the effects of ablating aNSCs on synaptic and cognitive functions in AD mice In this study, Sun and colleagues show that ablation of adult neural stem cells (aNSCs) improves cognitive functions in mouse models of Alzheimer disease (AD). This effect is associated with restoration of synaptic transmission in the dentate granule cells. Furthermore, alteration of calbindin is an important mediator between aNSC ablation and improved synaptic and cognitive functions in AD mice.
登录
查看更多内容
成年人类海马神经发生的动力学。
影响因子：
64.5
作者：
Spalding KL;Bergmann O;Alkass K;Bernard S;Salehpour M;Huttner HB;Boström E;Westerlund I;Vial C;Buchholz BA;Possnert G;Mash DC;Druid H;Frisén J
通讯作者：
Frisén J
影响因子：
6.1
作者：
Zhang, Heng;Zhang, Ling;Sun, Binggui
通讯作者：
Sun, Binggui
影响因子：
25
作者：
van Praag, H;Kempermann, G;Gage, FH
通讯作者：
Gage, FH
DOI：
10.1073/pnas.1001422107
发表时间：
2010-04-06
影响因子：
11.1
作者：
Wang, Jun Ming;Singh, Chanpreet;Brinton, Roberta Diaz
通讯作者：
Brinton, Roberta Diaz
影响因子：
82.9
作者：
You JC;Muralidharan K;Park JW;Petrof I;Pyfer MS;Corbett BF;LaFrancois JJ;Zheng Y;Zhang X;Mohila CA;Yoshor D;Rissman RA;Nestler EJ;Scharfman HE;Chin J
通讯作者：
Chin J