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学科主题: 基础医学
题名:
Elevation of Brain Magnesium Prevents and Reverses Cognitive Deficits and Synaptic Loss in Alzheimer′s Disease Mouse Model (Retracted article. See vol. 34, pg. 5733, 2014)
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, Guosong1,4
刊名: JOURNAL OF NEUROSCIENCE
发表日期: 2013-05-08
DOI: 10.1523/JNEUROSCI.4610-12.2013
卷: 33, 期:19, 页:8423-8441
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-BETA ; PLASTICITY ; CALCIUM ; DYSFUNCTION ; BACE1 ; NEUROPATHOLOGY ; TRANSMITTER
英文摘要:

Profound synapse loss is one of the major pathological hallmarks associated with Alzheimer′s disease (AD) and might underlie memory impairment. Our previous work demonstrated that the magnesium ion is a critical factor in controlling synapse density/plasticity. Here, we investigated whether elevation of brain magnesium by the use of a recently developed compound, magnesium-L-threonate (MgT), can ameliorate the AD-like pathologies and cognitive deficits in the APPswe/PS1dE9 mice, a transgenic (Tg) mouse model of AD. MgT treatment reduced A beta plaque and prevented synapse loss and memory decline in the Tg mice. Strikingly, MgT treatment was effective even when given to the mice at the end stage of their AD-like pathological progression. To explore how elevation of brain magnesium ameliorates the AD-like pathologies in the brains of Tg mice, we studied molecules critical for APP metabolism and signaling pathways implicated in synaptic plasticity/density. In the Tg mice, the NMDAR/CREB/BDNF signaling was downregulated, whereas calpain/calcineurin/Cdk5 neurodegenerative signaling and beta-secretase (BACE1) expression were upregulated. MgT treatment prevented the impairment of these signaling pathways, stabilized BACE1 expression, and reduced soluble APP beta and beta-C-terminal fragments in the Tg 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. Correlation studies suggested that the protection of NMDAR signaling might underlie the stabilization of BACE1 expression. Our results suggest that elevation of brain magnesium exerts substantial synap-toprotective effects in a mouse model of AD and may have therapeutic potential for treating AD in humans.

语种: 英语
所属项目编号: 2009CB941303 ; 2011CB302201 ; 2013CB835102 ; 30970957
项目资助者: National Basic Research Program of China ; National Natural Science Foundation of China
WOS记录号: WOS:000318775200030
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66910
Appears in Collections:基础医学院_神经生物学系_期刊论文

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作者单位: 1.Tsinghua Univ, Sch Med, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Beijing 100191, Peoples R China
3.Sun Yat Sen Univ, Zhongshan Sch Med, Dept Physiol, Guangzhou 510080, Guangdong, Peoples R China
4.Univ Texas Austin, Ctr Learning & Memory, Austin, TX 78712 USA

Recommended Citation:
Li, Wei,Yu, Jia,Liu, Yong,et al. Elevation of Brain Magnesium Prevents and Reverses Cognitive Deficits and Synaptic Loss in Alzheimer′s Disease Mouse Model (Retracted article. See vol. 34, pg. 5733, 2014)[J]. JOURNAL OF NEUROSCIENCE,2013,33(19):8423-8441.
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