北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 基础医学院  > 神经生物学系  > 期刊论文
学科主题: 基础医学
题名:
Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer′s disease mouse model
作者: Li, Wei1; Yu, Jia2; Liu, Yong3; Huang, Xiaojie1; Abumaria, Nashat1; Zhu, Ying1; Huang, Xian1; Xiong, Wenxiang1; Ren, Chi1; Liu, Xian-Guo3; Chui, Dehua2; Liu, Guosong1
关键词: Alzheimer&prime ; s disease ; Brain magnesium ; Synaptoprotection ; NMDAR signaling ; BACE1
刊名: MOLECULAR BRAIN
发表日期: 2014-09-13
DOI: 10.1186/s13041-014-0065-y
卷: 7, 期:1
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences
研究领域[WOS]: Neurosciences & Neurology
关键词[WOS]: NMDA RECEPTOR TRAFFICKING ; APP TRANSGENIC MICE ; MEMORY DEFICITS ; AMYLOID DEPOSITION ; BETA ; CALCIUM ; PLASTICITY ; MECHANISM ; NEUROPATHOLOGY ; TRANSMITTER
英文摘要:

Background: Profound synapse loss is one of the major pathological hallmarks associated with Alzheimer′s disease, which might underlie memory impairment. Our previous work demonstrates that magnesium ion is a critical factor in controlling synapse density/plasticity. Here, we tested whether elevation of brain magnesium, using a recently developed compound (magnesium-L-threonate, MgT), can ameliorate the AD-like pathologies and cognitive deficits in the APPswe/PS1dE9 mice, a transgenic mouse model of Alzheimer′s disease.

Results: MgT treatment reduced A beta-plaque, prevented synapse loss and memory decline in the transgenic mice. Strikingly, MgT treatment was effective even when the treatment was given to the mice at the end-stage of their Alzheimer′s disease-like pathological progression. To explore how elevation of brain magnesium ameliorates the AD-like pathologies in the brain of transgenic mice, we studied molecules critical for APP metabolism and signaling pathways implicated in synaptic plasticity/density. In the transgenic mice, the NMDAR signaling pathway was downregulated, while the BACE1 expression were upregulated. MgT treatment prevented the impairment of these signaling pathways, stabilized BACE1 expression and reduced sAPP beta and beta-CTF in the transgenic mice. At the molecular level, elevation of extracellular magnesium prevented the high A beta-induced reductions in synaptic NMDARs by preventing calcineurin overactivation in hippocampal slices.

Conclusions: Our results suggest that elevation of brain magnesium exerts substantial synaptoprotective effects in a mouse model of Alzheimer′s disease, and hence it might have therapeutic potential for treating Alzheimer′s disease.

语种: 英语
所属项目编号: 2009CB941303 ; 2011CB302201 ; 2013CB835102 ; 81270048/H3101 ; 30970957
项目资助者: National Basic Research Program of China (973 program) ; National Natural Science Foundation of China (NSFC)
WOS记录号: WOS:000342698800001
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56022
Appears in Collections:基础医学院_神经生物学系_期刊论文

Files in This Item:
File Name/ File Size Content Type Version Access License
Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer′s disease mouse model.pdf(2702KB)期刊论文出版稿限制开放 联系获取全文

作者单位: 1.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Beijing 100871, Peoples R China
3.Sun Yat Sen Univ, Zhongshan Sch Med, Dept Physiol, Guangzhou 510275, Guangdong, Peoples R China

Recommended Citation:
Li, Wei,Yu, Jia,Liu, Yong,et al. Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer′s disease mouse model[J]. MOLECULAR BRAIN,2014,7(1).
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Li, Wei]'s Articles
[Yu, Jia]'s Articles
[Liu, Yong]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Li, Wei]‘s Articles
[Yu, Jia]‘s Articles
[Liu, Yong]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace