Analysis of differential expression gene pattern and potential drugs in hippocampus of SAMP8 mice

LIU Tao; ZHANG Xuezhu; JIA Yujie; HAN Jingxian; NIE Kun

doi:10.3969/j.issn.1002-266X.2018.48.002

Abstract：ObjectiveTo analyze differential expression gene pattern in the hippocampus of senescence-accelerated mouse-prone 8 (SAMP8) mice and to predict the effective drugs by using network integrated public database of intracellular characteristics (LINCS).Methods Twenty two-month and 20 eight-month SAMP8 mice were selected as the acceleratedaging models of dementia, and SAMR1 mice at the same age were used as the controls of normal aging.Total RNA from hippocampus was used to Gene chip hybridization in mice.The LINCS database GEO2Enrichr was used to analyze the expression patterns of rapid aging genes in hippocampus of SAMP8 and SAMR1 mice, and the GO enrichment analysis of differentially expressed rapid aging genes was carried out to analyze the KEGG metabolic pathway.We used the CREEDS online analysis tool to qualitatively analyze the transcription pattern of rapid aging genes, and used small molecule drug modules to qualitatively analyze and predict the therapeutic drugs for senile dementia.Results Gene transcription pattern was characterized by up-regulation of gene expression in the SAMP8 mice of rapid aging, and gene transcription pattern was characterized by down-regulation of gene expression in SAMR1 mice of normal aging.GO enrichment analysis results showed that the up-regulated genes in SAMP8 mice were mainly located in the ribosome and mitochondria of cells, the main biological processes were the mechanism of protein synthesis, sorting, localization and viral nucleic acid synthesis in cells, and the main molecular function was NADH reductase activity.KEGG metabolic pathway analysis showed that the main pathways of metabolic network involved in the up-regulation of gene expression in hippocampus of SAMP8 mice were oxidative phosphorylation of mitochondria, 3 neurodegenerative pathways (Alzheimer's disease, Parkinson's disease and Huntington's disease) and ribosomal protein synthesis pathways, non-alcoholic fatty liver and Escherichia coli infection pathway.Qualitative analysis of gene transcription patterns showed that SAMP8 mice matched the single gene module Psap best and SAMR1 mice matched the single gene module Pink1 best.Qualitative analysis of small molecule drug modules showed that the most well-matched small molecule drug was vitamin PP.Conclusion Neuron protection is the main feature of gene expression in aged SAMP8 mice which is a special mitochondrial stress response mode (mt UPR).The expression of mitochondria-related genes was significantly up-regulated.Vitamin PP may be an effective drug for Alzheimer's disease.