阿尔茨海默病中的突触丧失：转基因小鼠模型双光子成像提供的机制性见解
Synaptic Loss in Alzheimer's Disease: Mechanistic Insights Provided by Two-Photon Imaging of Transgenic Mouse Models.
作者信息
Subramanian Jaichandar, Savage Julie C, Tremblay Marie-Ève
机构信息
Department of Pharmacology & Toxicology, University of Kansas, Lawrence, KS, United States.
Axe Neurosciences, Centre de Recherche du CHU de Québec, Université Laval, Québec City, QC, Canada.
出版信息
Front Cell Neurosci. 2020 Dec 17;14:592607. doi: 10.3389/fncel.2020.592607. eCollection 2020.
Abstract
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 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.
摘要
突触丧失是阿尔茨海默病认知衰退最密切的相关因素。利用表达人类家族性阿尔茨海默病突变基因的小鼠模型，对突触丧失背后的机制进行了广泛研究。在这篇综述中，我们总结了多光子成像如何增进了我们对活体动物大脑中与过量淀粉样蛋白相关的突触丧失机制的理解。我们还讨论了从这些成像研究中获得的证据，这些证据表明细胞内钙稳态失调以及小胶质细胞（大脑的免疫细胞）的细胞外活动在介导突触丧失中所起的作用。
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