中央杏仁核（CeA）是调控痛相关抑郁样情绪的关键脑区，组蛋白去乙酰化酶SIRTs在抑郁调节中具有重要作用。预实验提示，CeA谷氨酸能神经元中SIRT1可能参与调控CCI大鼠痛相关抑郁样情绪。研究显示，SIRT1可以诱导甲基化CpG结合蛋白2（MeCP2）赖氨酸464位点（K464）去乙酰化，减弱MeCP2对BDNF转录的抑制；预实验也显示，SIRT1激动剂可下调CeA中乙酰化MeCP2，上调BDNF表达。而BDNF是改善痛相关抑郁样情绪的重要因子。我们提出：CeA中SIRT1下调可促进MeCP2-K464乙酰化，增强MeCP2对BDNF转录的抑制，导致痛相关抑郁样情绪的发生。本项目拟应用CCI大鼠、SIRT1flox/flox和Mecp2-K464R小鼠等，研究CeA谷氨酸能神经元中SIRT1通过去乙酰化MeCP2-K464上调BDNF调控痛相关抑郁样情绪机制，为寻找防治药物提供新的思路。

Central amygdala (CeA) is a key brain region in the development of pain-related depression-like emotion. Histone deacetylase SIRTs have been reported to play important roles in depression. The results of our preliminary experiments suggested that SIRT1 in glutamatergic neurons of CeA may be related to pain-related depression-like emotion in chronic constriction injury (CCI)-induced neuropathic pain rats. It has been demonstrated that SIRT1 mediates the deacetylation of methyl-CpG binding protein 2 (MeCP2) at 464 lysine site (K464), thereby inhibiting MeCP2 binding to brain-derived neurotrophic factor (BDNF) promoter and upregulating BDNF. Our preliminary results showed that SIRT1 activator could decrease acetyl-MeCP2 expression, but increase BDNF expression. BDNF upregulation is demonstrated to alleviate pain-related depression-like emotion. Therefore, we hypothesize that the down-regulated SIRT1 expression in glutamatergic neurons of CeA could increase the acetylation of MeCP2-K464, promote MeCP2 binding to BDNF promoter, and inhibit the transcription of BDNF, leading to the development of pain-related depression-like emotion. Therefore, the current project is aimed to clarify the new mechanisms for SIRT1-mediated deacetylation of MeCP2-K464 and upregulation of BDNF in pain-related depression-like emotion, using CCI-induced neuropathic pain rats and SIRT1flox/flox mice as well as Mecp2-K464R mutant mice. This project will provide a new potential target for the discovery of analgesic drugs used to relieve pain-related depression-like emotion.