海马成体神经发生与抑郁症密切相关，而糖皮质激素受体（GR）对海马神经发生有重要调节作用，但调控机制尚不清楚。14-3-3蛋白与多种中枢神经系统功能紊乱密切相关。我们前期研究发现，高水平糖皮质激素诱导的抑郁模型中，海马14-3-3η水平增高，同时海马神经发生减弱，且GR磷酸化上升，GR核转运增强。然而14-3-3η调控GR确切的机制及在神经发生中的角色尚未阐明。因此，本项目应用神经行为学、分子生物学，结合CRISPR/Cas9、Cre/loxP和荧光可视技术，采用高水平糖皮质激素诱导的抑郁症小鼠模型，考察敲除/过表达海马神经干细胞中14-3-3η后，对GR磷酸化及核转运的影响，探究其与神经干细胞静息态、激活态、各分化阶段表达谱系的关系，分析对神经干细胞增殖、分化为新生神经元及突触形和功能的影响，阐明抑郁症中14-3-3η调控GR介导海马成体神经发生的机制，为探究神经发生的调控机制提供借鉴。

Recent research suggests that adult hippocampal neurogenesis closely links with depression, and glucocorticoid receptor plays an important role in regulating hippocampal neurogenesis. 14-3-3 protein closely links with many central nervous system disorders. Our previous studies showed that the level of 14-3-3η significantly increased in high corticosterone induced mouse model of depression, meanwhile, hippocampal neurogenesis significantly decreased, both GR phosphorylation and GR nuclear translocation enhanced. However the roles and mechanisms of 14-3-3η regulate glucocorticoid receptor has not been illuminated. So the present project applies CRISPR/Cas9, Cre/loxP and fluorescent visual technologies to knockout or overexpression 14-3-3η in neural stem cell of hippocampus in high corticosterone induced mouse model of depression, excavates the change of GR phosphorylation and GR nuclear translocation, investigates the effects of 14-3-3η on resting state, activated state and different differentiated state of neural stem cell, illustrates the effects of 14-3-3η on newborn neuron, synapsis morphology and function. It has great significance for this study to reveal the molecular mechanisms of 14-3-3η regulate glucocorticoid receptor mediated hippocampal neurogenesis and explore the regulation mechanism of neurogenesis.