GABA能神经系统功能失调是抑郁症发病机制之一，作为介导GABA能系统作用的一种代谢型受体，GABABR被发现在抑郁症中的作用至关重要。KCTD12是GABAB2R的辅助蛋白，既具有特异性调控GABAB2R功能的作用，又被筛查为罹患精神疾病的高风险因子，因此，KCTD12可能在抑郁症发病机制中发挥重要作用。我们已有结果提示，DG区KCTD12蛋白与抑郁症的发生高度相关，并影响该脑区的细胞增生和神经元活性。而神经发生与抑郁症发病密切相关，完整的GABABR信号也是维持正常DG脑区兴奋性所需。由此推测，慢性应激诱导DG区KCTD12蛋白过表达，特异性调控GABAB2受体功能，通过影响成年海马神经发生改变神经元兴奋性，介导抑郁样行为。本课题将结合基因、遗传学手段和电生理技术，阐明KCTD12作为GABAB2受体的辅助蛋白在抑郁症中的作用和机制，以期为抑郁症的药物研发提供依据。

Dysfunction of GABA nervous system is one of the pathogenesis of depression. As a metabolic receptor to mediate the action of GABA nervous system, GABABR has been found to play a crucial role in depression. As an auxiliary protein of GABAB2R, KCTD12 not only has a specific role in regulating GABAB2R function, but also is screened as a high-risk factor for mental illness. Therefore, KCTD12 may play an important role in the pathogenesis of depression. We have shown that KCTD12 protein in DG region is highly correlated with the occurrence of depression, and affects cell proliferation and neuron activity in this brain region. Neurogenesis is closely related to the onset of depression, and complete GABABR signal is required to maintain normal excitability of DG brain regions. It is speculated that chronic stress induces overexpression of KCTD12 protein in DG region, which specifically regulates GABAB2 receptor function, and mediates depression-like behavior by affecting adult hippocampal neurogenesis and changing neuron excitability. This project will combine gene, genetic means and electrophysiological technology to clarify the role and mechanism of KCTD12, as an auxiliary protein of GABAB2R in depression, in order to provide a basis for drug research and development of depression.