杏仁核O-连接的β-N-乙酰葡糖胺糖基化修饰对应激弹性的调节作用OACSTPCD

Objective To investigate the impact of O-linked β-N-acetylglucosamine(O-GlcNAc)modification levels in the amygdala on stress resilience.Methods A restraint stress model was established in male C57BL/6J mice by confining them for 24 hours,followed by by 7days of rest.Behavioral assays,including the tail suspension test,forced swimming test and fear conditioning test,were conducted.Subsequently,the mice were euthanized,and the hippocampus,cortex,and amygdala were isolated.O-GlcNAc modification levels in these brain regions were assessed using enzyme-linked immunosorbent assay(ELISA).Using stereotaxic brain injection techniques,the O-GlcNAcase(OGA)inhibitor,O-GlcNAc transferase(OGT)inhibitor,and OGA and OGT adeno-associated viruses were administered to regulate O-GlcNAc levels in the amygdala before their effects on stress-related behavior were observed.Results The restraint stress group showed significantly increased anxiety,depressive-like behavior,and impaired memory.Concomitantly,O-GlcNAc levels in the amygdala were significantly decreased post-stress and were negatively correlated with behavioral performance.Mice with higher stress resilience exhibited significantly higher levels of O-GlcNAc in the amygdala than more sensitive ones.Upregulation of O-GlcNAc levels in the amygdala via Thiamet-G or adeno-associated virus-O-GlcNAc transferaseinjections increased O-GlcNAc levels,alleviated depressive-like behavior and enhanced stress resilience.In contrast,downregulation of O-GlcNAc levels through OSMI-1 or adeno-associated virus-O-GlcNAcase injections reduced the O-GlcNAc levels,exacerbated depressive-like behavior and reduced resilience to stress.Conclusion O-GlcNAc modification levels in the amygdala play a critical role in regulating stress resilience following restraint stress in mice.