High-throughput Sequencing and Bioinformatics Analysis Reveals the Neurogenesis Key Targets of Curcumin Action in Mouse Brain with MCAO

Abstract

Background: Experimental studies have shown that Curcumin exerts neuroprotective effects in animal models with middle cerebral artery occlusion (MCAO). However, the mechanisms of protective effects of Curcumin in MCAO are not fully understood. Objective: This study aims to investigate the neurogenesis key targets of Curcumin action in mouse brain with MCAO. Methods: The MCAO models were established in mice. High-Throughput Sequencing was used to identify differentially expressed mRNA, lncRNA and circRNA. The reverse expressed mRNAs, lncRNA and circRNA in sham vs. MCAO and MCAO vs. Curcumin were identified. Biological functions were determined by gene ontology (GO) analyses. The protein-protein interaction (PPI) network of neurogenesis related genes was constructed. Next, neurogenesis related lncRNA/circRNA-miRNA-mRNA ceRNA network were constructed. Results: The total of reverse expressed 1215 mRNAs, 32 lncRNAs, and 43 circRNAs were filtered based on the 2 series (sham vs. MCAO and MCAO vs. Curcumin). The functional enrichment of 1215 reverse expressed mRNAs were involved in neurogenesis, generation of neurons, regulation of neurogenesis and others. The PPI network of neurogenesis related genes consisted of 115 nodes, and including Curcumin down regulated 27 genes and upregulated 36 genes. Further, the neurogenesis related lncRNA/circRNA-miRNA-mRNA ceRNAs network were constructed, and 5 lncRNA ceRNA network and 3 circRNA ceRNA network were explored. Conclusion: Our study revealed that Curcumin exerts neuroprotective effects by regulating neurogenesis. The neurogenesis related lncRNA/circRNA-miRNA-mRNA ceRNA network are potential therapeutic targets of Curcumin in MCAO. This study provided a theoretical basis for Curcumin exerts neuroprotective effects in MCAO.