Nodes and biological processes identified on the basis of network analysis in the brain of the senescence accelerated mice as an Alzheimer's disease animal model.
Nodes and biological processes identified on the basis of network analysis in the brain of the senescence accelerated mice as an Alzheimer's disease animal model.
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DOI：
10.3389/fnagi.2013.00065
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发表时间：
2013
影响因子：
4.8
通讯作者：
Zhang YX
中科院分区：
文献类型：
--
作者：
Cheng XR;Cui XL;Zheng Y;Zhang GR;Li P;Huang H;Zhao YY;Bo XC;Wang SQ;Zhou WX;Zhang YX
携带阿尔茨海默病（AD）的行为和组织病理学特征，衰老加速的小鼠倾向8（SAMP 8）小鼠目前被认为是用于研究AD的稳健模型。然而，SAMP 8小鼠与AD相关的潜在机制，优先途径和基因仍不清楚。在这项研究中，我们对SAMP 8小鼠的分子基础进行了生物学解释。我们的研究结果来自差异表达的基因在海马和大脑皮层的SAMP 8小鼠相比，年龄匹配的SAMR 1小鼠在2个月，6个月和12个月的年龄，使用cDNA微阵列分析。在PPI、MetaCore和共表达网络的基础上，我们在SAMP 8小鼠脑中构建了一个独特的遗传子网络。接下来，我们确定SAMP 8小鼠脑中突触传递和凋亡的调节被破坏。我们发现RAF 1、MAPT、PTGS 2、CDKN 2A、CAMK 2A、NTRK 2、AGER、ADRBK 1、MCM 3AP和STUB 1基因表达异常，这可能引发SAMP 8小鼠脑中生物过程的功能障碍。具体而言，我们发现了microRNA，包括miR-20 a，miR-17，miR-34 a，miR-155，miR-18 a，miR-22，miR-26 a，miR-101，miR-106 b和miR-125 b，可能调控子网络中节点的表达。总之，这些结果为SAMP 8小鼠的生物学和遗传机制提供了新的见解，并从系统的角度为我们理解SAMP 8小鼠的神经发病机制增加了一个重要方面。
Harboring the behavioral and histopathological signatures of Alzheimer's disease (AD), senescence accelerated mouse-prone 8 (SAMP8) mice are currently considered a robust model for studying AD. However, the underlying mechanisms, prioritized pathways and genes in SAMP8 mice linked to AD remain unclear. In this study, we provide a biological interpretation of the molecular underpinnings of SAMP8 mice. Our results were derived from differentially expressed genes in the hippocampus and cerebral cortex of SAMP8 mice compared to age-matched SAMR1 mice at 2, 6, and 12 months of age using cDNA microarray analysis. On the basis of PPI, MetaCore and the co-expression network, we constructed a distinct genetic sub-network in the brains of SAMP8 mice. Next, we determined that the regulation of synaptic transmission and apoptosis were disrupted in the brains of SAMP8 mice. We found abnormal gene expression of RAF1, MAPT, PTGS2, CDKN2A, CAMK2A, NTRK2, AGER, ADRBK1, MCM3AP, and STUB1, which may have initiated the dysfunction of biological processes in the brains of SAMP8 mice. Specifically, we found microRNAs, including miR-20a, miR-17, miR-34a, miR-155, miR-18a, miR-22, miR-26a, miR-101, miR-106b, and miR-125b, that might regulate the expression of nodes in the sub-network. Taken together, these results provide new insights into the biological and genetic mechanisms of SAMP8 mice and add an important dimension to our understanding of the neuro-pathogenesis in SAMP8 mice from a systems perspective.
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影响因子：
2.3
作者：
Chan SY;White K;Loscalzo J
通讯作者：
Loscalzo J
影响因子：
5.3
作者：
Canudas, AM;Gutierrez-Cuesta, J;Pallàs, M
通讯作者：
Pallàs, M
影响因子：
3.4
作者：
Cheng, Xiao-Rui;Zhou, Wen-Xia;Zhang, Yong-Xiang
通讯作者：
Zhang, Yong-Xiang
影响因子：
15.1
作者：
Delay C;Calon F;Mathews P;Hébert SS
通讯作者：
Hébert SS
DOI：
10.1073/pnas.0602266103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Costinean, S;Zanesi, N;Croce, CM
通讯作者：
Croce, CM