突触再生与神经再生是海马可塑性的重要组成。抑郁症的发生与海马BDNF水平低下引发的海马可塑性受损有密切联系。可可茶是以可可碱为优势生物碱的特殊茶组植物，民间认为有改善情绪的作用。我们的前期研究表明可可茶的活性成分可可碱能够改善抑郁行为，提高BDNF表达，促进神经再生，但具体机制尚不明确。本项目拟建立慢性温和不可预知应激抑郁小鼠模型和成年小鼠神经干细胞模型，采用双光子显微镜活体成像、激光共聚焦和透射电镜等多种成像技术检测突触形态和超微结构变化，并对突触标志蛋白表达与神经电生理进行检测，BrdU免疫组化检测神经元增殖与分化，研究可可碱促进突触再生与神经再生的作用；以X-射线辐射阻断海马神经再生小鼠模型，探讨突触再生与神经再生之间的关系，及对抑郁的影响；采用RNAi技术研究BDNF对突触再生和神经再生的作用。本项目有望阐明可可碱通过提高BDNF水平，促进突触再生和神经再生，改善抑郁的作用机制。

Synaptogenesis and neurogenesis are both important to hippocampal plasticity. Recent studies have suggested that hippocampus BDNF-deficient impaired hippocampal plasticity was closely linked to depression. Camellia ptilophylla, a special tea plant with abundant content of theobromine, is thought to have a positive effect on mood management. Our pilot study has shown that theobromine, a purine alkaloids obtained from C. ptilophylla, is a potent anti-depressant. Moreover, theobromine treatment had enhanced the expression of BDNF and restored hippocampal neurogenesis. However, the mechanism of theobromine-improved depressive behavior is still unclear. Therefore, the purpose of this project is to examine the effect of theobromine on promotion of synaptogenesis and neurogenesis by utilizing chronic unpredicted mild stress mice model and adult neural stem cell models. We will employ two photon microscopy, laser-scanning confocal microscopy and transmission electron microscopy to directly analyze the morphology and ultramicrostructures of synapses. The expression of synaptic protein and the electroneurophysiology will also be detected. By using BrdU labeling, the neurogenesis effect of theobromine will be evaluated in vivo and in vitro. A hippocampal neurogenesis suppression model with X-ray irradiation will also be established to investigate the relation between neurogenesis and synaptogenesis; and compare their impact on depression. Finally, using RNA interference-based loss-of-function study, we will explore the mechanism of theobromine-promoted neurogenesis and synaptogenesis through BDNF mediation. This project will provide scientific evidences for the BDNF up-regulating mechanism of theobromine on the treatment for depression through promoting neurogenesis and synaptogenesis.