抑郁症是一类高度异质性、负担承重的慢性脑疾病，但病因仍不完全清楚。最近临床研究和动物模型实验表明，抑郁症伴随着免疫系统功能显著改变。我们前期表达谱芯片发现抑郁症患者外周血细胞因子ENA78差异表达最为显著（下调），并通过两独立样本验证，然其中枢水平不明。但已有研究显示中枢ENA78增加参与了神经元退行凋亡过程，我们预实验也发现抑郁模型大鼠海马ENA78表达上调。本项目拟研究ENA78与抑郁症之间的相互关系。利用慢性不可预知温和应激抑郁症动物模型（CUMS）试图回答抑郁症是否存在中枢ENA78表达上调，并利用大鼠慢病毒转染验证ENA78表达上调是否导致抑郁样行为，探讨中枢ENA78表达上调导致神经元结构与功能的改变,同时探讨外周EAN78水平是否受HPA轴反馈调节而表现为下调，抗抑郁症药物文拉法辛改善临床症状的同时是否下调ENA78。该研究可为临床抑郁症的生物学诊断和治疗提供新思路和新途径。

Major depressive disorder (MDD) is a chronic brain disease with high heterogeneity and economic burden, however, the etiology is still not very clear. Recently, clinical and animal studies showed that immune system function significantly changed accompanied with MDD. Our previous study demonstrated that ENA78 was the most differentially expressed (down-regulated) immune inflammatory factors through whole genomic cRNA microarray, followed with validation in two independent larger samples, however, ENA78 levels of CNS in patients with MDD is unknown. Previous studies have shown that increasing ENA78 levls in CNS was involved in the process of neuron apoptosis; and our preliminary study demonstrated that ENA78 was upregulated in hippocampus of stress depression rats. The aim of the present study is to explore the relationship between ENA78and MDD. To answer whether central ENA78 is upregulated in MDD through chronic unpredictable mild stress animal model of depression (CUMS); whether peripheral ENA78 level is downregulated by the feedback regulation of HPA axis; whether venlafaxine improve clinical symptoms while downregulating ENA78. Furthermore, we explore whether the rat can display depression-like behavior through central lentiviral transfection for overexpression of ENA78; and whether it can lead to the change of the neurons structure and function. The present research could provide new idea and new breakthrough for biological diagnosis and treatment of MDD.