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.
Keywords: Alzheimer's disease, senescence accelerated mouse prone 8, molecular network, hippocampus, cerebral cortex, differential expressed genes, synaptic transmission, apoptosis
Citation: Cheng X-r, Cui X-l, Zheng Y, Zhang G-r, Li P, Huang H, Zhao Y-y, Bo X-c, Wang S-q, Zhou W-x and Zhang Y-x (2013) 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. Front. Aging Neurosci. 5:65. doi: 10.3389/fnagi.2013.00065
Received: 05 September 2013; Accepted: 10 October 2013;
Published online: 29 October 2013.
Edited by:Cheng-xin Gong, The City University of New York, USA
Reviewed by:José M. Delgado-García, University Pablo de Olavide, Seville, Spain
Copyright © 2013 Cheng, Cui, Zheng, Zhang, Li, Huang, Zhao, Bo, Wang, Zhou and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Wen-xia Zhou and Yong-xiang Zhang, Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian district, Beijing 100850, China e-mail: firstname.lastname@example.org; email@example.com
†These authors have contributed equally to this work.