Antiepileptic Effects of Inhibitors of MiR-92b-3p in Animal Models of Alzheimer's Disease Complicated by Epilepsy
Objective To evaluate the antiepileptic effect of miR-92b-3p inhibitor in Alzheimer's disease(AD)animal model with epilepsy.Methods Regulatory molecules of a disintegrin and metalloprotease 10(ADAM10)were screened using bioinformatics methods and dual-luciferase assays.The expression levels of miR-92b-3p and ADAM10 in neuronal cells and animal models of AD with epilepsy were evaluated using real-time quantitative polymerase chain reaction and Western blot.Finally,miR-92b-3p inhibitors were administered via nasal administration to assess their antiepileptic effects in AD induced epilepsy animal models.Results By bioinformatics methods,dual-luciferase assay,Western blot bands and grayscale analysis,it was confirmed that miR-92b-3p could post-transcriptionally regulate ADAM10,and had a strong regulatory effect on ADAM10 in neuronal cells.MiR-92b-3p was significantly upregulated in AD complicated epilepsy animal model(AD+EP)group compared with AD animal model group.Compared with AD+EP group,the incidence of epilepsy,the incidence of Racine grade 4 or higher were significantly reduced,and the latency of Racine grade 4 or higher seizures was significantly prolonged in the treatment group given miR-92b-3p inhibitor intranasally.Conclusion In this study,we preliminarily confirmed that the inhibitor of miR-92b-3p has an antiepileptic effect in an animal model of AD complicated with epilepsy.