Ablating Adult Neural Stem Cells Improves Synaptic and Cognitive Functions in Alzheimer Models
| Autor: | Xiaojie Wei, Xiaoqin Zhang, Jing Wang, Yang He, Yufei Mei, Guoping Peng, Dongming Zhou, Hao-Wei Shen, Benyan Luo, Enlu Yang, Binggui Sun, Qiang Shu, Yu-Dong Zhou, Dongpi Wang, Xuekun Li |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
cognitive functions adult neural stem cells Neuropathology Hippocampal formation Biology Neurotransmission Biochemistry Calbindin Article 03 medical and health sciences 0302 clinical medicine calbindin Genetics medicine synaptic transmission mouse Dentate gyrus Neurogenesis Cell Biology Alzheimer's disease medicine.disease Neural stem cell 030104 developmental biology Neuroscience 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem Cell Reports |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2020.12.003 |
| Popis: | Summary 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. Highlights • 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. |
| Databáze: | OpenAIRE |
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