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Inhibiting Adult Neurogenesis Ameliorates Synaptic and Cognitive Deficits in Animal Models of Alzheimer’s Disease

54 Pages Posted: 11 Apr 2018 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

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

Xiaojie Wei

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

Mingkai Wang

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

Yufei Mei

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

Hongyu Pan

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

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

Adult-born new neurons are associated with a variety of cognitive functions. Previous studies have indicated that adult neurogenesis is disturbed in the brain of Alzheimer's disease (AD) patients and animal models. However, whether and how newborn neurons affect the neuropathology in AD is not clear. Here, we found that genetic or drug induced ablation of adult-born new neurons significantly ameliorated synaptic and cognitive impairments in APP/PS1 and hAPP-J20 mice, two commonly used mouse models of AD. Furthermore, inhibiting adult neurogenesis did not affect the levels of soluble amyloid β (Aβ), the deposition of amyloid plaques, and the proteolytic cleavage of hAPP but increased the activity of hippocampal granule cells. Taken together, our study demonstrates beneficial effects of inhibiting adult neurogenesis on AD pathology, and these effects were caused presumably by improving the activity of granule cells in the dentate gyrus but not by reducing Aβ levels in brains of AD mice.

Suggested Citation

Zhang, Xiaoqin and He, Yang and Wang, Dongpi and Wei, Xiaojie and Wang, Mingkai and Zhou, Dongming and Mei, Yufei and Pan, Hongyu and Zhou, Yudong and Sun, Binggui, Inhibiting Adult Neurogenesis Ameliorates Synaptic and Cognitive Deficits in Animal Models of Alzheimer’s Disease (2018). Available at SSRN: https://ssrn.com/abstract=3155654 or http://dx.doi.org/10.2139/ssrn.3155654
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

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

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

Mingkai 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

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

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

Hongyu Pan

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

Hangzhou, Zhejiang Province 310058
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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