Impaired neurogenesis, neuronal loss, and brain functional deficits in the APPxPS1-Ki mouse model of Alzheimer's disease
Impaired neurogenesis, neuronal loss, and brain functional deficits in the APPxPS1-Ki mouse model of Alzheimer's disease
复制标题
DOI：
10.1016/j.neurobiolaging.2009.03.009
复制
发表时间：
2011-03-01
影响因子：
4.2
通讯作者：
Delatour, B.
中科院分区：
文献类型：
--
作者：
Faure, A.;Verret, L.;Delatour, B.
在阿尔茨海默病患者的脑中积累的淀粉样β肽物质被认为具有神经毒性作用，因此是这种神经退行性疾病的生理病理学中的关键因素。我们研究了一种新的小鼠突变体（APPxPS 1-Ki）系，该系与大多数转基因模型相比，出现早发性脑淀粉样蛋白β沉积和随后的神经元损失。在6个月大的小鼠中，我们观察到海马体中的细胞层萎缩，以及通过磁共振成像在体内测量的神经发生和脑血流灌注减少的急剧减少。在这些小鼠中，神经功能障碍和空间海马依赖性记忆缺陷也得到证实，并随着年龄的增长而恶化。我们在这里描述了一个表型的APPxPS 1-Ki小鼠，总结了几个神经解剖学的改变和功能缺陷唤起人类病理学。这种具有较强表面效度的转基因模型可能对未来AD的病理生理学和治疗学研究非常有益。(C)2009 Elsevier Inc. All rights reserved.
Amyloid-beta peptide species accumulating in the brain of patients with Alzheimer's disease are assumed to have a neurotoxic action and hence to be key actors in the physiopathology of this neurodegenerative disease. We have studied a new mouse mutant (APPxPS1-Ki) line developing both early-onset brain amyloid-beta deposition and, in contrast to most of transgenic models, subsequent neuronal loss. In 6-month-old mice, we observed cell layer atrophies in the hippocampus, together with a dramatic decrease in neurogenesis and a reduced brain blood perfusion as measured in vivo by magnetic resonance imaging. In these mice, neurological impairments and spatial hippocampal dependant memory deficits were also substantiated and worsened with aging. We described here a phenotype of APPxPS1-Ki mice that summarizes several neuroanatomical alterations and functional deficits evocative of the human pathology. Such a transgenic model that displays strong face validity might be highly beneficial to future research on AD physiopathogeny and therapeutics. (C) 2009 Elsevier Inc. All rights reserved.