A non-transgenic mouse model (icv-STZ mouse) of Alzheimer's disease: similarities to and differences from the transgenic model (3xTg-AD mouse).
A non-transgenic mouse model (icv-STZ mouse) of Alzheimer's disease: similarities to and differences from the transgenic model (3xTg-AD mouse).
复制标题
DOI：
10.1007/s12035-012-8375-5
复制
发表时间：
2013-04
影响因子：
5.1
通讯作者：
Gong, Cheng-Xin
中科院分区：
文献类型：
--
作者：
Chen, Yanxing;Liang, Zhihou;Blanchard, Julie;Dai, Chun-Ling;Sun, Shenggang;Lee, Moon H.;Grundke-Iqbal, Inge;Iqbal, Khalid;Liu, Fei;Gong, Cheng-Xin
阿尔茨海默病（AD）可分为散发性AD（SAD）和家族性AD（FAD）。大多数AD病例是散发性的，由多种病因因素引起，包括环境、遗传和代谢因素，而FAD是由早老素或淀粉样蛋白-β（Aβ）前体蛋白（APP）基因突变引起的。AD的常用动物模型是3xTg-AD转基因小鼠模型，其携带突变的早老素1、APP和tau基因，因此代表FAD的模型。在表征代表不同AD机制的动物模型的领域中存在未满足的需求，使得可以在这些动物模型中临床前评估SAD的潜在药物。通过脑室内（icv）给药链脲佐菌素（STZ）产生的小鼠模型（icv-STZ小鼠）显示了SAD的许多方面。在这项研究中，我们比较了icv-STZ小鼠和3xTg-AD小鼠之间的非认知和认知行为以及生化和免疫组化改变。我们发现，这两种小鼠模型都表现出探索活动增加以及学习和空间记忆受损。这两种模型还显示了神经炎症，突触蛋白和胰岛素/IGF-1（胰岛素样生长因子-1）信号的改变，以及大脑中过度磷酸化tau蛋白的增加。在icv-STZ小鼠中最突出的脑异常是神经炎症，而在3xTg-AD小鼠中是过度磷酸化tau的升高。这些观察结果证明了icv-STZ小鼠和3xTg-AD小鼠模型之间的行为和神经病理学相似性和差异，并将有助于指导未来使用这两种小鼠模型开发AD药物的研究。
Alzheimer’s disease (AD) can be divided into sporadic AD (SAD) and familial AD (FAD). Most AD cases are sporadic and result from multiple etiologic factors, including environmental, genetic and metabolic factors, whereas FAD is caused by mutations in the presenilins or amyloid-β (Aβ) precursor protein (APP) genes. A commonly used animal model for AD is the 3xTg-AD transgenic mouse model, which harbors mutated presenilin 1, APP and tau genes and thus represents a model of FAD. There is an unmet need to in the field to characterize animal models representing different AD mechanisms, so that potential drugs for SAD can be evaluated preclinically in these animal models. A mouse model generated by intracerebroventricular (icv) administration of streptozocin (STZ), the icv-STZ mouse, shows many aspects of SAD. In this study, we compared the non-cognitive and cognitive behaviors as well as biochemical and immunohistochemical alterations between the icv-STZ mouse and the 3xTg-AD mouse. We found that both mouse models showed increased exploratory activity as well as impaired learning and spatial memory. Both models also demonstrated neuroinflammation, altered synaptic proteins and insulin/IGF-1 (insulin-like growth factor-1) signaling, and increased hyperphosphorylated tau in the brain. The most prominent brain abnormality in the icv-STZ mouse was neuroinflammation, and in the 3xTg-AD mouse it was elevation of hyperphosphorylated tau. These observations demonstrate the behavioral and neuropathological similarities and differences between the icv-STZ mouse and the 3xTg-AD mouse models and will help guide future studies using these two mouse models for the development of AD drugs.
登录
查看更多内容
DOI：
10.1016/j.jalz.2010.04.006
发表时间：
2010-09
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Iqbal K;Grundke-Iqbal I
通讯作者：
Grundke-Iqbal I
影响因子：
3.1
作者：
Dhull, Dinesh Kumar;Jindal, Ankur;Padi, Satyanarayana S. V.
通讯作者：
Padi, Satyanarayana S. V.
影响因子：
8.2
作者：
Gimenez-Llort, L.;Blazquez, G.;Fernandez-Teruel, A.
通讯作者：
Fernandez-Teruel, A.
影响因子：
4.7
作者：
Gruenblatt, Edna;Salkovic-Petrisic, Melita;Hoyer, Siegfried
通讯作者：
Hoyer, Siegfried
小胶质细胞激活与增强的肿瘤坏死因子-Alpha和单核细胞化学吸收剂蛋白-1表达的早期相关性在三重转基因阿尔茨海默氏病小鼠的内嗅皮层中特异性。
影响因子：
9.3
作者：
Janelsins, Michelle C.;Mastrangelo, Michael A.;Oddo, Salvatore;LaFerla, Frank M.;Federoff, Howard J.;Bowers, William J.
通讯作者：
Bowers, William J.