Effects Of Aldosterone On Hippocampal Neurogenesis And Cognitive Function After Surgery In Aged Mice

Objective: Hippocampal neurogenesis is closely related to learning and memory,and hippocampal neurogenesis disorders are involved in the development of many neurodegenerative diseases.Mineralocorticoid receptor(MR)plays a vital role in regulating stress response,neuroendocrine and cognitive functions,and is involved in regulating the integrity and stability of neural networks.However,the potential role of MR in the pathogenesis of postoperative cognitive dysfunction(POCD)is unclear.Therefore,in order to explore the action and mechanism of MR on hippocampal neurogenesis and cognitive function in elderly mice,and to provide new targets and experimental evidence for the understanding and treatment of POCD,we use behavioral and molecular biology methods to detect and analyze postoperative cognitive function,neurogenesis,and expression of PI3K/AKT/GSK-3? signaling pathway-related proteins in elderly mice.Methods: 1.In the present study,Mice were randomly dividedinto 5 groups: Control group(C group),Surgery group(S group),Surgery+ Aldosterone group(S+ALDO group),Surgery + Wortmannin group(S+WORT group),Surgery + Aldosterone + Wortmannin group(S+ALDO+WORT group).Immediately after surgery,mice were injected intraperitoneally with aldosterone(100ug / kg)and / or wortmannin(1mg/ kg);One day before the sacrifice,mice were injected intraperitoneally with BrdU(100 mg / kg / time,3 times in total).2.Morris water maze and open field tests were performed to detect the learning and memory of mice at 1 ? 3 ? 7 and 14 days after surgery,analyzing the effects of aldosterone on learning and memory function of elderly mice after surgery.3.Immunofluorescence was used to detect the number of BrdU +,Nestin +,BrdU / Nestin + positive cells in the hippocampal dentate gyrus of mice at 1?3?7 and 14 days after surgery,analyzing the effect of aldosterone on hippocampal neurogenesis in aged mice after surgery.4.To explore the related mechanism of aldosterone regulating hippocampal neurogenesis and cognitive function of aged mice,Western-blot was used to detect PI3K/AKT/GSK-3? signaling pathway related proteins AKT,p-AKT,GSK-3?,P-GSK-3? expression,immunofluorescence was used to detect hippocampal neurogenesis,Morris Water maze test and open field test were used to detect learning and memory.Results: 1.Morris water maze test results showed that surgical stress increased the escape latency,reduced the number of crossingplatform and the time spent in the target quadrant;open field test results showed that surgical stress reduced the number of crossing and rearing.However,aldosterone treatment improved the performance of mice in Morris water maze test and open field tests,and the improvement was most pronounced on 3 days after surgery.2.Immunofluorescence results showed that surgical stress significantly reduced the number of BrdU /Nestin + cells in the dentate gyrus of hippocampus,while aldosterone treatment significantly increased the number of BrdU / Nestin + cells in the dentate gyrus of hippocampus on 3 and 7 days after surgery.3.Western-Blot results showed that surgical stress significantly inhibited the phosphorylation of AKT and GSK-3? protein in the hippocampus and the proliferation of hippocampal neural stem cells,and impaired postoperative cognitive function.Aldosterone treatment promoted the expression of P-AKT and P-GSK-3? proteins,promoted the proliferation of hippocampal neural stem cells,as well as improved postoperative cognitive function.However,wortmannin treatment significantly reversed these effects of aldosterone.Conclusion: Aldosterone improved hippocampal neurogenesis and cognitive dysfunction after surgery in aged mice,and the mechanism may be related to activation of PI3K/AKT/GSK-3? signaling.