Sub-anaesthetic doses of Esketamine ameliorate memory impairment in Alzheimer's disease by regulating the BDNF/AKT/mTOR signaling pathway in rats

Abstract

Abstract Backgroud In this study, we aimed to investigate the effect and mechanism of action of Esketamine on Alzheimer's disease (AD) related memory impairment. Methods and Results We investigated the effect of Esketamine on an STZ and D-galactose(D-gal)-induced AD model in rats. After the Morris water maze tested the learning and spatial memory ability, the Western-blot method detected the contents of phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) in the hippocampus. HE staining was used to observe the pathological changes in the CA3 region of the hippocampus, the expression of BDNF was detected by immunohistochemistry, and ELISA detected the contents of Aβ42 and phosphorylated tau protein (p-tau). Taking Esketamine after treatment, 1 the Results of MWM: the escape latency of the mice was shortened, and the number of crossing the platform was increased; 2 Western blot results: the expression of p-AKT and p-mTOR was up-regulated. 3 HE results: cell number increase, more closely, deep into the nucleus is still visible; 4 Immunohistochemical results showed that the expression of BDNF increased; 5 ELISA results: decreased levels of Aβ42 and p-tau. Conclusions Sub-anesthetic dose of Esketamine can reduce the level of Aβ42 and the hyperphosphorylation of tau protein through BDNF/AKT/mTOR pathway in AD rats, thereby reducing the neuropathological damage of the hippocampus and improving the learning and spatial memory ability.