Dendritic vulnerability in neurodegenerative disease: insights from analyses of cortical pyramidal neurons in transgenic mouse models.
Dendritic vulnerability in neurodegenerative disease: insights from analyses of cortical pyramidal neurons in transgenic mouse models.
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DOI：
10.1007/s00429-010-0244-2
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发表时间：
2010-03
影响因子：
3.1
通讯作者：
Hof, Patrick R.
中科院分区：
文献类型：
--
作者：
Luebke, Jennifer I.;Weaver, Christina M.;Rocher, Anne B.;Rodriguez, Alfredo;Crimins, Johanna L.;Dickstein, Dara L.;Wearne, Susan L.;Hof, Patrick R.
在神经退行性疾病如阿尔茨海默病中，神经元树突和树突棘经历显著的病理变化。由于这些高度动态的结构在单个神经元的信号传导中以及最终在介导认知功能的神经元网络的功能中的决定性作用，因此对这些变化的详细理解是至关重要的。已经开发了突变鼠模型，例如Tg2576 APP突变小鼠和rTg4510 tau突变小鼠，以提供对涉及淀粉样蛋白和tau蛋白的异常产生和聚集的发病机制的深入了解，因为这些蛋白在神经变性疾病中起关键作用。这篇综述展示了我们的合作小组采取的多维方法，以增加对神经退行性疾病的病理机制的理解，使用这些小鼠模型。这种方法包括使用共聚焦激光扫描显微镜和全细胞膜片钳记录技术，结合计算建模方法，从额叶皮质锥体神经元获得的经验3D形态和电生理数据的分析。这些合作研究旨在阐明新皮层神经元营养不良变化的影响，定义相关神经退行性疾病模型中差异神经元脆弱性的细胞表型，并为开发旨在预防，逆转或补偿痴呆神经退行性变化的有意义的治疗策略提供基础。
In neurodegenerative disorders, such as Alzheimer’s disease, neuronal dendrites and dendritic spines undergo significant pathological changes. Because of the determinant role of these highly dynamic structures in signaling by individual neurons and ultimately in the functionality of neuronal networks that mediate cognitive functions, a detailed understanding of these changes is of paramount importance. Mutant murine models, such as the Tg2576 APP mutant mouse and the rTg4510 tau mutant mouse have been developed to provide insight into pathogenesis involving the abnormal production and aggregation of amyloid and tau proteins, because of the key role that these proteins play in neurodegenerative disease. This review showcases the multidimensional approach taken by our collaborative group to increase understanding of pathological mechanisms in neurodegenerative disease using these mouse models. This approach includes analyses of empirical 3D morphological and electrophysiological data acquired from frontal cortical pyramidal neurons using confocal laser scanning microscopy and whole-cell patch-clamp recording techniques, combined with computational modeling methodologies. These collaborative studies are designed to shed insight on the repercussions of dystrophic changes in neocortical neurons, define the cellular phenotype of differential neuronal vulnerability in relevant models of neurodegenerative disease, and provide a basis upon which to develop meaningful therapeutic strategies aimed at preventing, reversing, or compensating for neurodegenerative changes in dementia.
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影响因子：
5.3
作者：
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通讯作者：
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