Amyloid pathology-produced unexpectedmodifications of calcium homeostasis in hippocampal subicular dendrites
Amyloid pathology-produced unexpectedmodifications of calcium homeostasis in hippocampal subicular dendrites
复制标题
DOI：
10.1016/j.jalz.2019.07.017
复制
发表时间：
2020-02-01
影响因子：
14
通讯作者：
Moreno, Herman
中科院分区：
文献类型：
--
作者：
Angulo, Sergio L.;Henzi, Thomas;Moreno, Herman
阿尔茨海默病（AD）与神经元钙平衡失调有关，钙平衡失调与神经网络高兴奋性有关。钙结合蛋白cal- binding - d - 28k （CB）的表达降低可能是AD的一个易感因素。在阿尔茨海默病早期，由于未知的原因，耻骨下受到影响。方法：在AD中，采用CB敲除和对照小鼠的荧光Ca2+成像联合膜片钳来表征Ca2+动力学，静息Ca2+和Ca2+缓冲能力。还分析了野生型和AD小鼠的CB表达水平。结果：野生型小鼠的骨下和齿状回出现与年龄相关的CB表达下降，在AD小鼠中未见。静息Ca2+和Ca2+缓冲能力在老年AD小鼠的树突下增加。模型表明，AD钙的变化可以通过Ca2+挤压泵的改变来解释，而不是通过缓冲液。讨论：总体而言，AD患者Ca2+稳态异常与年龄相关，包括代偿过程。
Introduction: Alzheimer's disease (AD) is linked to neuronal calcium dyshomeostasis, which is associated with network hyperexcitability. Decreased expression of the calcium-binding protein cal-bindin-D-28K (CB) might be a susceptibility factor for AD. The subiculum is affected early in AD, for unknown reasons.Methods: In AD, CB knock-out and control mice fluorescence Ca2+ imaging combined with patch clamp were used to characterize Ca2+ dynamics, resting Ca2+, and Ca2+-buffering capacity in subicular neurons. CB expression levels in wild-type and AD mice were also analyzed.Results: The subiculum and dentate gyrus of wild-typemice showed age-related decline in CB expression not observed in AD mice. Resting Ca2+ and Ca2+-buffering capacity was increased in aged AD mice subicular dendrites. Modeling suggests that AD calcium changes can be explained by alterations of Ca2+ extrusion pumps rather than by buffers.Discussion: Overall, abnormal Ca2+ homeostasis in AD has an age dependency that comprises multiplemechanisms, including compensatory processes.