14-3-3η介导自噬在小柴胡汤促神经发生抗抑郁中的作用及机制

抑郁症发病机制复杂，成体神经发生与抗抑郁药的药效密切相关。自噬对神经发生有重要调节作用，已有报道14-3-3可调控自噬。我们前期研究发现皮质酮抑郁模型（CORT）中，海马齿状回14-3-3η表达降低，伴随神经发生明显减弱。小柴胡汤显著改善抑郁样行为，增加14-3-3η表达，恢复神经发生，降低自噬相关蛋白的表达，且对自噬上游PI3K/Akt、MAPK/ERK信号通路均有激活作用。然而，自噬在小柴胡汤促神经发生抗抑郁中扮演何种角色，小柴胡汤可否通过14-3-3η调控自噬，这些问题尚不清楚。基于此，项目应用神经行为学、免疫荧光方法，结合基因编辑技术，采用CUMS和CORT抑郁小鼠模型，考察小柴胡汤对抑郁动物海马齿状回原有神经元、神经干细胞、新生神经元形态及功能的影响，探究自噬在小柴胡汤促神经发生抗抑郁中的作用及机制，阐明14-3-3η在小柴胡汤调控自噬中的分子机制，为小柴胡汤治疗抑郁症提供借鉴。

The pathogenesis of depression is complex. Adult neurogenesis is closely related to the efficacy of antidepressants. Autophagy plays an important role in neurogenesis. 14-3-3 has been reported to regulate autophagy. In our previous study, we found that the expression of 14-3-3η in dentate gyrus of hippocampus was decreased in corticosterone depression model (CORT), accompanied by decreasing neurogenesis. Xiaochaihutang could significantly improve depression-like behaviors, increase the expression of 14-3-3η, restore neurogenesis, decrease the expression of autophagy-related proteins and activate the PI3K/Akt and MAPK/ERK signaling pathways upstream of autophagy. However, the role of autophagy in the neurogenesis of xiaochaihutang and whether xiaochaihutang could regulate autophagy through 14-3-3η were unclear. Based on this, the project used behaviors, immunofluorescence and gene editing technology to investigate the effect of xiaochaihutang on the morphology and function of the original neurons, neural stem cells and newborn neurons in the dentate gyrus of the hippocampus in CUMS and CORT depressed animals, to explore the role and mechanism of autophagy in promoting neurogenesis of xiaochaihutang, and to clarify the role of 14-3-3η in xiaochaihutang regulated the function and molecular mechanism of autophagy, which provided reference for xiaochaihutang in the treatment of depression.