Involvement of Scratch2 in GalR1-mediated depression-like behaviors in the rat ventral periaqueductal gray.

Proceedings of the National Academy of Sciences of the United States of America 2021 Jun 15

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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.

Citation

Yutao Yang, Yueting Li, Bo Liu, Chenchen Li, Zijin Liu, Jiahui Deng, Hanjiang Luo, Xiaoxiao Li, Jinjin Wu, Hui Li, Chuan-Yue Wang, Ming Zhao, Haohao Wu, Francois Lallemend, Per Svenningsson, Tomas G M Hökfelt, Zhi-Qing David Xu. Involvement of Scratch2 in GalR1-mediated depression-like behaviors in the rat ventral periaqueductal gray. Proceedings of the National Academy of Sciences of the United States of America. 2021 Jun 15;118(24)