气候变化领域集成服务门户(CCPortal): Involvement of Scratch2 in GalR1-mediated depression-like behaviors in the rat ventral periaqueductal gray

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DOI	10.1073/pnas.1922586118
	Involvement of Scratch2 in GalR1-mediated depression-like behaviors in the rat ventral periaqueductal gray
	Yang Y.; Li Y.; Liu B.; Li C.; Liu Z.; Deng J.; Luo H.; Li X.; Wu J.; Li H.; Wang C.-Y.; Zhao M.; Wu H.; Lallemend F.; Svenningsson P.; Hökfelt T.G.M.; Xu Z.-Q.D.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:24
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Galanin; Neuropeptides; Stress; Transcription factor; Transmitter coexistence
语种	英语
scopus关键词	4 aminobutyric acid; galanin receptor 1; glutamic acid; messenger RNA; transcription factor; transcription factor Scratch2; unclassified drug; 4 aminobutyric acid receptor; galanin receptor 1; glutamic acid; protein binding; transcription factor; adult; animal tissue; Article; brain nerve cell; controlled study; depression; down regulation; GalR1 gene; gene expression level; gene knockdown; in vitro study; in vivo study; nonhuman; pathogenesis; physiological stress; promoter region; protein expression; rat; ventrolateral periaqueductal gray; animal; animal behavior; complication; depression; E box element; gene expression regulation; genetics; mental stress; metabolism; pathology; PC12 cell line; periaqueductal gray matter; transcription initiation site; Animals; Behavior, Animal; Depression; E-Box Elements; GABAergic Neurons; Gene Expression Regulation; Glutamic Acid; PC12 Cells; Periaqueductal Gray; Promoter Regions, Genetic; Protein Binding; Rats; Receptor, Galanin, Type 1; Stress, Psychological; Transcription Factors; Transcription Initiation Site
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251150
作者单位	Department of Neurobiology, Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100069, China; Department of Pathology, Capital Medical University, Beijing, 100069, China; Beijing Key Laboratory of Epilepsy, Sanbo Brain Hospital, Capital Medical University, Beijing, 100069, China; Anding Hospital, Capital Medical University, Beijing, 100088, China; Department of Neuroscience, Karolinska Institutet, Stockholm, SE-17177, Sweden; Center for Molecular Medicine, Department of Neurology and Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, Stockholm, SE-17176, Sweden
推荐引用方式 GB/T 7714	Yang Y.,Li Y.,Liu B.,et al. Involvement of Scratch2 in GalR1-mediated depression-like behaviors in the rat ventral periaqueductal gray[J],2021,118(24).
APA	Yang Y..,Li Y..,Liu B..,Li C..,Liu Z..,...&Xu Z.-Q.D..(2021).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,118(24).
MLA	Yang Y.,et al."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 118.24(2021).