title: 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.
abstract: 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.
authors.affiliation: Department of Neuroimmunopharmacology, Beijing Institute of Pharmacology and Toxicology Beijing, China.
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Cheng
authors.forename: Xiu-Liang
authors.initials: XL
authors.lastname: Cui
authors.forename: Yue
authors.initials: Y
authors.lastname: Zheng
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Huang
authors.initials: H
authors.lastname: Huang
authors.forename: Yue-Ying
authors.initials: YY
authors.lastname: Zhao
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Bo
authors.forename: Sheng-Qi
authors.initials: SQ
authors.lastname: Wang
authors.forename: Wen-Xia
authors.initials: WX
authors.lastname: Zhou
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Zhang
keywords: Alzheimer's disease; apoptosis; cerebral cortex; differential expressed genes; hippocampus; molecular network; senescence accelerated mouse prone 8; synaptic transmission