抑郁症发病机制至今未能确切阐明。抑郁症发病中伴有氧化应激水平升高和体内抗氧化剂减少。维生素C是体内重要的抗氧化物，近年来还发现其具有独特的表观遗传学功能，可通过TET酶依赖的途径参与DNA的去甲基化过程并影响相关转录本水平。申请者发现：在CUS所致小鼠抑郁模型中，海马等脑区维生素C氧化降解增加，其转运蛋白SVCT2介导的稳态调控机制也发生异常。同时我们发现，维生素C具有良好的抗抑郁活性，其机制可能和DNA去甲基化酶TET1依赖的BDNF基因转录增加有关。因此，应激条件下维生素C稳态失衡可能是抑郁症发生的重要机制。本项目拟综合运用药理学、动物行为学、分子生物学、生物分析化学、电子自旋共振波谱等方法，探索维生素C及其转运体SVCT2功能障碍在抑郁发生中的作用及机制，筛选重建脑内维生素C稳态调控机制的药物并评估其抗抑郁效应，为阐明抑郁症的发生机制和开发新型的抗抑郁剂提供思路和技术支持。

The precise mechanism underlay depression is poorly understood yet. Increased oxidative stress and reduced endogenous antioxidants may underlay the mechanism for depression. Vitamine c is an important endogenous anti-oxidant. Recently, the epigenetic role of vitamine c has been revealed. Vitamine c is essential for TET1-dependent DNA demethylatio, which may regulate the transcript level. We observed that in a chronic unpredictable mild stress (CUS)-induced depressive model, a decrease of vitamine c content was observed, and the SVCT2-dependent homeostasis of vitamine c was impaired. We also found vitamine c exhibited a good anti-depressant activity, which may act through maintaining TET1-dependent DNA demethylation of BDNF gene. Thus, the impairments of vitamine c homeostasis may be involved in the depressive behaviors. Here, we investigated the role of vitamine c and SVCT2 in the stress-induced depressive behaviors in combination of pharmacological approaches, behavior experiments, molecular biology, biochemical analytical chemistry and Electron Paramagnetic Resonance technology. We also screened for drugs that rebuild the vitamine c homeostasis. Our study may provide new mechanism and therapeutic approaches for depression .