Improvement effect of olaxetan on autistic mice by regulating the AKT/GSK-3β signaling pathway
Objective To explore the improvement effect of oxiracetam(ORC)on autism mice by regulating the pro-teinkinase B(AKT)/glycogen synthase kinase-3β(GSK-3β)signaling pathway.Methods Autistic pregnant mice were estab-lished by injecting valproic acid(VPA),and male offspring were selected as the study subjects.The successfully modeled offspring were randomly grouped into VPA group,ORC-L group,ORC-H group,ORC-H+LY294002 group,with 10 mice in each group.Male offspring from normal pregnant mice injected with physiological saline were used as the blank group.Social interaction and preference abilities were evaluated.The marbles bury experiment was applied to detect repetitive stereotyped behavior.New object experiment was applied to evaluate learning and memory abilities.H-E staining was applied to observe pathological damage in hippocampal tissue.Reagent kits were applied to detect oxidative stress indicators such as superoxide dismutase(SOD),catalase(CAT),and malondialdehyde(MDA)levels in frontal lobe tissue.Western blot was applied to detect the expression of AKT/GSK-3β signaling pathway related proteins and brain derived neurotrophic factor(BDNF)protein.Results Compared with the blank group,the social interaction index,social preference index,recognition index,SOD,CAT levels,BDNF,p-GSK-3β/GSK-3β,and p-AKT/AKT expression of mice in the VPA group were greatly reduced,the number of buried marbles and MDA level were greatly increased(P＜0.05).Compared with VPA group,the above indexes in ORC-L group and ORC-H group were reversed,and there were differences among groups(P＜0.05).LY294002 reversed the improving effects of ORC-H on autistic mice.Conclusion ORC improves symptoms in autistic mice by regulating the AKT/GSK-3βsignaling pathway.
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