Downregulation of hippocampal SIRT6 activates AKT/CRMP2 signaling and ameliorates chronic stress-induced depression-like behavior in mice

• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2020,（12）
• 所属期刊栏目: Article Neuropharmacology
• 页码范围: 1557-1567
• 页数: 11页
• 语种: 英文

摘要

Sirtuin 6 (SIRT6) has been reported to play a key role in cognitive function and mood regulation,yet its role in mood disorders is not completely understood.Here,we confirmed that knockdown of hippocampal SIRT6 alleviated depression-like behaviors induced by chronic unpredictable stress (CUS) in mice.Our in vitro data showed that SIRT6 negatively regulated protein kinase B (AKT) signaling by deacetylating histone 3 at Lys9 and Lys56.Knockdown of SIRT6 significantly increased AKT phosphorylation activity,while decreased collapsin response mediator protein 2 (CRMP2) phosphorylation activity.Furthermore,pharmacologic inhibition of SIRT6 by ferulic acid (FA) (40 or 80 mg· kg-1 per day,i.g.) could activate AKT/CRMP2 pathway in vitro,which has been proved to exert an antidepressant-like effect on CUS-induced depresslve models.In conclusion,our study suggested that hippocampal SIRT6 contributes to the performance of depression-like behaviors by suppressing AKT/CRMP2 signaling,and FA ameliorates CUS-induced depression-like behaviors in mice as a potential pharmacologic inhibitor of SIRT6.