lncRNA-Associated Competitive Endogenous RNA Regulatory Network in an Aβ25-35-Induced AD Mouse Model Treated with Tripterygium Glycoside

Background: Tripterygium glycoside (TG) has been suggested to have protective effects on the diseases of the central nervous system including Alzheimer's disease (AD). The mechanisms involving lncRNA-associated competing endogenous RNAs (ceRNAs) were shown to play important roles in the development of AD. However, the ceRNA mechanism of TG in treating AD is still unknown. Thus, we aimed to explore the ceRNA mechanism in the treatment of AD with TG. Methods: A total of 32 C57BL/6J mice were administered 3 mu L of A beta(25-35) (dual side, 1 mg/ mL) by a single stereotactic injection in the brain to conduct AD mouse model. AD mouse models were randomly selected and divided into the AD+normal saline (NS) group (n=16) and the AD+TG group (n=16). The expression data of lncRNAs, mRNAs, and miRNAs in the hippocampus of mice from AD+NS group (n=3) and the AD+TG group (n=3) were obtained by microarray analysis. The MuTaME method was used to predict the ceRNA regulatory network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the DAVID database. A protein-protein interaction (PPI) network was constructed by using STRING software. Results: TG can significantly improve spatial memory and inhibit the production of p-tau in an A beta(25-35)-induced AD mouse model. A total of 661 differentially expressed lncRNAs, 503 mRNAs, and 13 miRNAs were identified. A ceRNA network involving the top 200 mRNAmiRNA-lncRNA pairs with 16 lncRNAs, 11 miRNAs, and 52 mRNAs was visualized. And a PPI network complex filtered 26 gene nodes in DEGs was predicted. Conclusion: We have identified 503 DEGs, 661 DElncRNAs, and 13 DEmiRNAs during treatment with TG in A beta(25-35)-induced AD mouse model. A ceRNA network based on the DElncRNAs, DEmRNAs, and DEmiRNAs was conducted, which provided new insight into the lncRNA-mediated ceRNA regulatory mechanisms underlying the effects of TG in the treatment of AD.

Automated summary

In an Aβ(25-35)-induced AD mouse model, Tripterygium glycoside can significantly improve spatial memory and inhibit the production of p-tau. Microarray analysis revealed changes in the expression of lncRNAs, mRNAs, and miRNAs in the hippocampus of mice treated with TG, and a ceRNA network and PPI network were established.