Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer's disease

被引：241

作者：

Chen, Jing-Fei ^{[1
,4
]}

Liu, Kun ^{[1
,4
]}

Hu, Bo ^{[2
,4
]}

Li, Rong-Rong ^{[2
]}

Xin, Wendy ^{[3
]}

Chen, Hao ^{[4
]}

Wang, Fei ^{[1
]}

Chen, Lin ^{[1
]}

Li, Rui-Xue ^{[1
]}

Ren, Shu-Yu ^{[1
]}

Xiao, Lan ^{[1
]}

Chan, Jonah R. ^{[3
]}

Mei, Feng ^{[1
]}

机构：

[1] Third Mil Med Univ, Dept Histol & Embryol, Brain & Intelligence Res Key Lab, Chongqing Educ Commiss, Chongqing 400038, Peoples R China

[2] Third Mil Med Univ, Chongqing Key Lab Neurobiol, Brain & Intelligence Res Key Lab Chongqing Educ C, Dept Physiol, Chongqing 400038, Peoples R China

[3] Univ Calif San Francisco, Dept Neurol, UCSF Weill Inst Neurosci, San Francisco, CA 94158 USA

[4] Third Mil Med Univ, Coll Basic Med Sci, Experimental Ctr Bas Med, Chongqing 400038, Peoples R China

来源：

NEURON | 2021年 / 109卷 / 14期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

WHITE-MATTER HYPERINTENSITIES; SHARP-WAVE-RIPPLE; MULTIPLE-SCLEROSIS; MOUSE MODEL; MICE; REMYELINATION; INTEGRITY; DEFICITS; OLIGODENDROCYTES; PATHOLOGY;

D O I：

10.1016/j.neuron.2021.05.012

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Severe cognitive decline is a hallmark of Alzheimer's disease (AD). In addition to gray matter loss, significant white matter pathology has been identified in AD patients. Here, we characterized the dynamics of myelin generation and loss in the APP/PS1 mouse model of AD. Unexpectedly, we observed a dramatic increase in the rate of new myelin formation in APP/PS1 mice, reminiscent of the robust oligodendroglial response to demyelination. Despite this increase, overall levels of myelination are decreased in the cortex and hippo campus of APP/PS1 mice and postmortem AD tissue. Genetically or pharmacologically enhancing myelin renewal, by oligodendroglial deletion of the muscarinic M1 receptor or systemic administration of the promyelinating drug clemastine, improved the performance of APP/PS1 mice in memory-related tasks and increased hippocampal sharp wave ripples. Taken together, these results demonstrate the potential of enhancing myelination as a therapeutic strategy to alleviate AD-related cognitive impairment.

引用

页码：2292 / +

页数：22

共 69 条

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