Synaptic Loss in Alzheimer's Disease: Mechanistic Insights Provided by Two-Photon in vivo Imaging of Transgenic Mouse Models

被引：63
作者：
Subramanian, Jaichandar [1 ]
Savage, Julie C. [2 ,7 ]
Tremblay, Marie-Eve [3 ,4 ,5 ,6 ]
机构：
[1] Univ Kansas, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA
[2] Univ Laval, Axe Neurosci, Ctr Rech, CHU Quebec, Quebec City, PQ, Canada
[3] McGill Univ, Neurol & Neurosurg Dept, Montreal, PQ, Canada
[4] Univ Laval, Dept Mol Med, Quebec City, PQ, Canada
[5] Univ Victoria, Div Med Sci, Victoria, BC, Canada
[6] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC, Canada
[7] Convelo Therapeut, Cleveland, OH USA
来源：
FRONTIERS IN CELLULAR NEUROSCIENCE | 2020年 / 14卷
基金：
加拿大健康研究院; 美国国家卫生研究院;
关键词：
dendritic spines; microglia; two-photon; in vivo imaging; amyloid mouse models; AMYLOID-PRECURSOR-PROTEIN; DENDRITIC SPINE LOSS; A-BETA; CALCIUM HOMEOSTASIS; MICROGLIAL ACTIVATION; BOUTON NUMBER; MICE; PLAQUES; SECRETASE; DYSREGULATION;
D O I：
10.3389/fncel.2020.592607
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Synapse loss is the strongest correlate for cognitive decline in Alzheimer's disease. The mechanisms underlying synapse loss have been extensively investigated using mouse models expressing genes with human familial Alzheimer's disease mutations. In this review, we summarize how multiphoton in vivo imaging has improved our understanding of synapse loss mechanisms associated with excessive amyloid in the living animal brain. We also discuss evidence obtained from these imaging studies for the role of cell-intrinsic calcium dyshomeostasis and cell-extrinsic activities of microglia, which are the immune cells of the brain, in mediating synapse loss.
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页数：13
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