Entorhinal cortical defects in Tg2576 mice are present as early as 2-4 months of age.
Entorhinal cortical defects in Tg2576 mice are present as early as 2-4 months of age.
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DOI：
10.1016/j.neurobiolaging.2014.07.001
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发表时间：
2015-01
影响因子：
4.2
通讯作者：
Scharfman HE
中科院分区：
文献类型：
--
作者：
Duffy AM;Morales-Corraliza J;Bermudez-Hernandez KM;Schaner MJ;Magagna-Poveda A;Mathews PM;Scharfman HE
内嗅皮层(EC)是阿尔茨海默病(AD)最早显示神经病理的脑区之一。一种模拟淀粉样蛋白β(Aβ)神经病理的小鼠模型Tg2576小鼠被用来解决这些早期变化。在这里，我们显示EC异常发生在2-4个月大的Tg2576小鼠中，这是在β-淀粉样蛋白沉积之前的一个年龄，以前的研究表明那里几乎没有行为障碍。首先，我们使用夹心ELISA法证明，在2个月大的Tg2576小鼠的EC中可以检测到可溶性人Aβ40和Aβ42，在β淀粉样蛋白沉积之前。然后，我们证明了2-4个月大的Tg2576小鼠在物体放置时受到损害，这是一种依赖EC的认知任务。接下来，我们发现在2-4个月大的Tg2576小鼠中，NeuN的表达和髓鞘摄取的缺陷发生在EC的浅层。在含有EC的Tg2576小鼠的切片中，有单个刺激对潜在白质诱发的重复场电位，以及对细胞外镁([Mg2+]o)减少的更大反应，这表明兴奋性增加。然而，与野生型小鼠相比，Tg2576小鼠深层神经元逆行激活的潜伏期更长。结果表明，EC在早期就发生了变化，并表明兴奋性的改变发生在广泛的斑块病理之前。
The entorhinal cortex (EC) is one of the first brain areas to display neuropathology in Alzheimer’s disease (AD). A mouse model which simulates amyloid-β (Aβ) neuropathology, the Tg2576 mouse, was used to address these early changes. Here we show EC abnormalities occur in 2–4 month-old Tg2576 mice, an age prior to β-amyloid deposition and where previous studies suggest that there are few behavioral impairments. First we show, using sandwich ELISA, that soluble human Aβ40 and Aβ42 are detectable in the EC of 2-month-old Tg2576 mice prior to β-amyloid deposition. We then demonstrate that 2–4 month-old Tg2576 mice are impaired at object placement, an EC-dependent cognitive task. Next we show that defects in NeuN expression and myelin uptake occur in the superficial layers of the EC in 2–4-month-old Tg2576 mice. In slices from Tg2576 mice that contained the EC, there were repetitive field potentials evoked by a single stimulus to the underlying white matter, and a greater response to reduced extracellular magnesium ([Mg2+]o), suggesting increased excitability. However, deep layer neurons in Tg2576 mice had longer latencies to antidromic activation than wild type mice. The results show changes in the EC at early ages, and suggest that altered excitability occurs before extensive plaque pathology.
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影响因子：
3.3
作者：
Duffy, A. M.;Zhou, P.;Milner, T. A.;Pickel, V. M.
通讯作者：
Pickel, V. M.
影响因子：
3.1
作者：
Canto CB;Wouterlood FG;Witter MP
通讯作者：
Witter MP
影响因子：
2.7
作者：
ENNACEUR, A;DELACOUR, J
通讯作者：
DELACOUR, J
影响因子：
4.8
作者：
De Felice, Fernanda G.;Velasco, Pauline T.;Klein, William L.
通讯作者：
Klein, William L.
影响因子：
5.3
作者：
Duffy, Aine M.;Schaner, Michael J.;Scharfman, Helen E.
通讯作者：
Scharfman, Helen E.