Galanin receptor1 (GalR1) transcript levels are elevated in the rat ventral periaqueductal gray (vPAG) after chronic mild stress (CMS) and are related to depression-like behavior. To explore the mechanisms underlying the elevated GalR1 expression, we carried out molecular biological experiments in vitro and in animal behavioral experiments in vivo. It was found that a restricted upstream region of the GalR1 gene, from −250 to −220, harbors an E-box and plays a negative role in the GalR1 promoter activity. The transcription factor Scratch2 bound to the E-box to down-regulate GalR1 promoter activity and lower expression levels of the GalR1 gene. The expression of Scratch2 was significantly decreased in the vPAG of CMS rats. Importantly, local knockdown of Scratch2 in the vPAG caused elevated expression of GalR1 in the same region, as well as depression-like behaviors. RNAscope analysis revealed that GalR1 mRNA is expressed together with Scratch2 in both GABA and glutamate neurons. Taking these data together, our study further supports the involvement of GalR1 in mood control and suggests a role for Scratch2 as a regulator of depression-like behavior by repressing the GalR1 gene in the vPAG.

慢性轻度应激 (CMS) 后大鼠腹侧导水管周围灰质 (vPAG) 中甘丙肽受体 1 (GalR1) 转录水平升高，并且与抑郁样行为有关。为了探索 GalR1 表达升高的机制，我们进行了体外分子生物学实验和体内动物行为实验。发现GalR1基因的上游受限区域，从 -250 到 -220，带有一个 E-box 并在GalR1启动子活性中起负面作用。转录因子 Scratch2 与 E-box 结合以下调GalR1启动子活性并降低GalR1的表达水平基因。CMS大鼠vPAG中Scratch2的表达明显降低。重要的是，vPAG 中 Scratch2 的局部敲除导致同一区域 GalR1 的表达升高，以及抑郁样行为。RNAscope 分析显示GalR1 mRNA 与Scratch2 一起在GABA 和谷氨酸神经元中表达。综合这些数据，我们的研究进一步支持 GalR1 参与情绪控制，并表明 Scratch2 通过抑制 vPAG 中的GalR1基因作为抑郁样行为的调节剂的作用。