The development of adult neural stem cells (aNSCs) was impaired in the hippocampus of animal models of Alzheimer’s disease (AD). However, whether and how aNSCs and new neurons derived from aNSCs affect AD neuropathology is unclear. Here, we found that genetic or drug-induced ablation of aNSCs significantly ameliorated deficits of synaptic plasticity and cognitive functions in two mouse models of AD. On the other hand, whole cell recording revealed that deleting aNSCs prevented the increased inhibition in the dentate granule cells of AD mice. Furthermore, deleting aNSCs did not affect Aβ levels but prevented the calbindin depletion in the hippocampus of AD mice. Knocking down calbindin in the hippocampus abolished the effects of deleting aNSCs on synaptic and cognitive functions in AD mice. Taken together, our data suggest that deleting aNSCs improved synaptic plasticity and cognitive functions in AD mice by regulating the activity of dentate granule cells via calbindin.
Zhang, Xiaoqin and Mei, Yufei and He, Yang and Wang, Dongpi and Yang, Enlu and Wei, Xiaojie and Zhou, Dongming and Wang, Jing and Shen, Haowei and Shu, Qiang and Zhou, Yudong and Sun, Binggui, Deleting Adult Neural Stem Cells Ameliorates Synaptic and Cognitive Deficits in Animal Models of Alzheimer's Disease (April 26, 2019). Available at SSRN: https://ssrn.com/abstract=3378284 or http://dx.doi.org/10.2139/ssrn.3378284
This version of the paper has not been formally peer reviewed.
Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province ( email )
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