Circ-gabra5 exacerbates cognitive impairment in Alzheimer’s disease mice by regulating AKT through miR-455-3p

Abstract Objective TTo explore the role of circ-gabra5 in the pathogenesis of Alzheimer’s disease (AD) in mice. Methods APP/PS1 double transgenic AD mice (6 months old) were selected as the experimental group, and C57BL/6 wild-type (WT) mice were enrolled as the control group. The mice were divided into an AD group and an AD mice with circ-gabra5 knockout (AD+circ-gabra5 knockout) group, with 5 mice in each group. After total RNA was extracted from mouse brain, differential expression of circRNA was detected, and real-time quantitative PCR (RT-qPCR) was used to validate the top 6 circRNA genes with differences. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Using hippocampal stereo injection of lentivirus to knock out the circ-gabra5 gene, the learning and memory function of mice was detected with Morris water maze test, and the number of Aβ plaques in mouse brain tissue was observed through immunohistochemistry. Transmission electron microscopy was utilized to observe the mitochondrial damage and synaptic count in mouse neurons. Dual luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay were employed to verify the interaction between circ-gabra5 and miR-455-3p. Western blotting was apllied to detect the expression level of AKT protein. Results There were 273 differentially expressed genes screened between AD mice and WT mice, including 163 up-regulated and 110 down-regulated genes. Circ-gabra5 had the largest fold difference of 1.39 (P