Modulating adult neurogenesis affects synaptic plasticity and cognitive functions in mouse models of Alzheimer's disease

Xiaoqin Zhang; Xiaojie Wei; Yufei Mei; Dongpi Wang; Jing Wang; Yiping Zhang; Xuekun Li; Yan Gu; Guoping Peng; Binggui Sun

doi:10.1016/j.stemcr.2021.11.003

Modulating adult neurogenesis affects synaptic plasticity and cognitive functions in mouse models of Alzheimer's disease

Stem Cell Reports. 2021 Dec 14;16(12):3005-3019. doi: 10.1016/j.stemcr.2021.11.003. Epub 2021 Dec 2.

Authors

Xiaoqin Zhang¹, Xiaojie Wei², Yufei Mei², Dongpi Wang³, Jing Wang², Yiping Zhang², Xuekun Li⁴, Yan Gu⁵, Guoping Peng², Binggui Sun⁶

Affiliations

¹ Department of Physiology and Pharmacology, Medical School of Ningbo University, Ningbo, Zhejiang Province 315211, China.
² Department of Neurobiology and Department of Neurology of the First Affiliated Hospital, Zhejiang University School of Medicine, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.
³ Department of Neurobiology and Department of Neurology of the First Affiliated Hospital, Zhejiang University School of Medicine, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310058, China; Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310003, China.
⁴ Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310003, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310029, China.
⁵ Center for Stem Cell and Regenerative Medicine and Department of Neurology of the Second Affiliated Hospital, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
⁶ Department of Neurobiology and Department of Neurology of the First Affiliated Hospital, Zhejiang University School of Medicine, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310058, China. Electronic address: bsun@zju.edu.cn.

Abstract

New neurons are abnormal in the adult hippocampus of Alzheimer's disease (AD) mouse models. The effects of modulating adult neurogenesis on AD pathogenesis differ from study to study. We reported recently that ablation of adult neural stem cells (aNSCs) was associated with improved memory in AD models. Here, we found that long-term potentiation (LTP) was improved in the hippocampus of APP/PS1 mice after ablation of aNSCs. This effect was confirmed in hAPP-J20 mice, a second AD mouse model. On the other hand, we found that exposure to enriched environment (EE) dramatically increased the number of DCX⁺ neurons, promoted dendritic growth, and affected the location of newborn neurons in the dentate gyrus of APP/PS1 mice, and EE exposure significantly ameliorated memory deficits in APP/PS1 mice. Together, our data suggest that both inhibiting abnormal adult neurogenesis and enhancing healthy adult neurogenesis could be beneficial for AD, and they are not mutually exclusive.

Keywords: Alzheimer's disease; adult neurogenesis; mouse; spatial memory; synaptic plasticity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / pathology*
Alzheimer Disease / physiopathology*
Amyloid beta-Protein Precursor / metabolism
Animals
CA1 Region, Hippocampal / pathology
CA1 Region, Hippocampal / physiopathology
Cognition / physiology*
Dentate Gyrus / metabolism
Disease Models, Animal
Gene Deletion
Humans
Long-Term Potentiation
Mice, Transgenic
Neural Stem Cells / metabolism
Neurogenesis / physiology*
Neuronal Plasticity / physiology*
Presenilin-1 / metabolism
Proto-Oncogene Proteins c-fos / metabolism
Receptors, GABA-A / metabolism
Spatial Memory

Substances

Amyloid beta-Protein Precursor
Presenilin-1
Proto-Oncogene Proteins c-fos
Receptors, GABA-A