Brain gene expression of a sporadic (icv-STZ Mouse) and a familial mouse model (3xTg-AD mouse) of Alzheimer's disease.
Brain gene expression of a sporadic (icv-STZ Mouse) and a familial mouse model (3xTg-AD mouse) of Alzheimer's disease.
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DOI：
10.1371/journal.pone.0051432
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gong CX
中科院分区：
文献类型：
--
作者：
Chen Y;Tian Z;Liang Z;Sun S;Dai CL;Lee MH;LaFerla FM;Grundke-Iqbal I;Iqbal K;Liu F;Gong CX
阿尔茨海默病(AD)分为散发性AD(SAD)和家族性AD(FAD)。大多数AD是散发性的，可能是多种病因引起的，包括环境、遗传和代谢因素，而FAD是由早老素或淀粉样蛋白(Aβ，Aβ)前体蛋白(APP)突变引起的。一种常用的AD小鼠模型是3xTg-AD小鼠，它是由突变的早老素1、APP和tau在大脑中过度表达而产生的，因此代表了FAD的小鼠模型。通过脑室注射链脲佐菌素(STZ)建立的小鼠模型ICV-STZ小鼠，显示了SAD的许多方面。尽管这两个模型被广泛用于AD研究，但它们之间的基因表达差异尚不清楚。在这里，我们使用定制的qPCR阵列比较了84个AD相关基因在ICV-STZ小鼠和3xTg-AD小鼠的海马区和大脑皮层中的表达。这些基因涉及APP加工、tau/细胞骨架、突触功能、细胞凋亡和自噬、AD相关蛋白激酶、葡萄糖代谢、胰岛素信号转导和mTOR途径。我们发现，在这两种小鼠模型中，大约有20个基因的表达发生了变化，这影响了上述每一类基因。这些基因改变中的许多与先前在AD大脑中观察到的一致。在这两个模型的小鼠的海马区，这些改变的基因中的大多数表达都减少或有减少的趋势。在这两种AD模型小鼠的大脑皮质中，发现基因表达的显著差异。在3xTg-AD小鼠中，与突触功能相关的基因表达异常较多，而在ICV-STZ小鼠中，与胰岛素信号和糖代谢相关的基因表达下调。本研究提供了这两种AD小鼠模型的重要基础知识，并将有助于指导未来利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 may result from multiple etiologic factors, including environmental, genetic and metabolic factors, whereas FAD is caused by mutations of presenilins or amyloid-β (Aβ) precursor protein (APP). A commonly used mouse model for AD is 3xTg-AD mouse, which is generated by over-expression of mutated presenilin 1, APP and tau in the brain and thus represents a mouse model of FAD. A mouse model generated by intracerebroventricular (icv) administration of streptozocin (STZ), icv-STZ mouse, shows many aspects of SAD. Despite the wide use of these two models for AD research, differences in gene expression between them are not known. Here, we compared the expression of 84 AD-related genes in the hippocampus and the cerebral cortex between icv-STZ mice and 3xTg-AD mice using a custom-designed qPCR array. These genes are involved in APP processing, tau/cytoskeleton, synapse function, apoptosis and autophagy, AD-related protein kinases, glucose metabolism, insulin signaling, and mTOR pathway. We found altered expression of around 20 genes in both mouse models, which affected each of above categories. Many of these gene alterations were consistent with what was observed in AD brain previously. The expression of most of these altered genes was decreased or tended to be decreased in the hippocampus of both mouse models. Significant diversity in gene expression was found in the cerebral cortex between these two AD mouse models. More genes related to synaptic function were dysregulated in the 3xTg-AD mice, whereas more genes related to insulin signaling and glucose metabolism were down-regulated in the icv-STZ mice. The present study provides important fundamental knowledge of these two AD mouse models and will help guide future studies using these two mouse models for the development of AD drugs.
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影响因子：
3.8
作者：
de la Monte SM
通讯作者：
de la Monte SM
影响因子：
14
作者：
通讯作者：
--
影响因子：
4.7
作者：
Gruenblatt, Edna;Salkovic-Petrisic, Melita;Hoyer, Siegfried
通讯作者：
Hoyer, Siegfried
影响因子：
3.5
作者：
Hutton, M;Hardy, J
通讯作者：
Hardy, J
DOI：
10.3233/jad-2011-101989
发表时间：
2011
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Barnett A;Brewer GJ
通讯作者：
Brewer GJ