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Deleting Adult Neural Stem Cells Ameliorates Synaptic and Cognitive Deficits in Animal Models of Alzheimer's Disease

68 Pages Posted: 3 May 2019 Sneak Peek Status: Review Complete

See all articles by Xiaoqin Zhang

Xiaoqin Zhang

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Yufei Mei

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Yang He

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Dongpi Wang

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Enlu Yang

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Xiaojie Wei

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Dongming Zhou

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Jing Wang

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Haowei Shen

Ningbo University - Department of Physiology and Pharmacology

Qiang Shu

Zhejiang University - Children's Hospital

Yudong Zhou

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Binggui Sun

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

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Abstract

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.

Keywords: Alzheimer's disease, adult neural stem cells, synaptic plasticity, learning and memory, mouse

Suggested Citation

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). NEURON-D-19-00532. Available at SSRN: https://ssrn.com/abstract=3378284 or http://dx.doi.org/10.2139/ssrn.3378284
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Xiaoqin Zhang

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Hangzhou, Zhejiang Province 310058
China

Yufei Mei

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Hangzhou, Zhejiang Province 310058
China

Yang He

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Hangzhou, Zhejiang Province 310058
China

Dongpi Wang

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Hangzhou, Zhejiang Province 310058
China

Enlu Yang

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Hangzhou, Zhejiang Province 310058
China

Xiaojie Wei

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Hangzhou, Zhejiang Province 310058
China

Dongming Zhou

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Hangzhou, Zhejiang Province 310058
China

Jing Wang

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province

Hangzhou, Zhejiang Province 310058
China

Haowei Shen

Ningbo University - Department of Physiology and Pharmacology

Ningbo, 315211
China

Qiang Shu

Zhejiang University - Children's Hospital

Hangzhou
China

Yudong Zhou

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province ( email )

Hangzhou, Zhejiang Province 310058
China

Binggui Sun (Contact Author)

Zhejiang University - Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province ( email )

Hangzhou, Zhejiang Province 310058
China

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