@article{db4dffcee7ca4603a6fc02fcf78b081e,
title = "A Brain Signaling Framework for Stress-Induced Depression and Ketamine Treatment Elucidated by Phosphoproteomics",
abstract = "Depression is a common affective disorder characterized by significant and persistent low mood. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, is reported to have a rapid and durable antidepressant effect, but the mechanisms are unclear. Protein phosphorylation is a post-translational modification that plays a crucial role in cell signaling. Thus, we present a phosphoproteomics approach to investigate the mechanisms underlying stress-induced depression and the rapid antidepressant effect of ketamine in mice. We analyzed the phosphoprotein changes induced by chronic unpredictable mild stress (CUMS) and ketamine treatment in two known mood control centers, the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc). We initially obtained >8,000 phosphorylation sites. Quantitation revealed 3,988 sites from the mPFC and 3,196 sites from the NAc. Further analysis revealed that changes in synaptic transmission-related signaling are a common feature. Notably, CUMS-induced changes were reversed by ketamine treatment, as shown by the analysis of commonly altered sites. Ketamine also induced specific changes, such as alterations in synapse organization, synaptic transmission, and enzyme binding. Collectively, our findings establish a signaling framework for stress-induced depression and the rapid antidepressant effect of ketamine.",
keywords = "LC-MS/MS, brain signaling, chronic unpredictable mild stress (CUMS), depression, ketamine, phosphoproteomics",
author = "Yan Xiao and Huoqing Luo and Yang, {Wen Z.} and Yeting Zeng and Yinbo Shen and Xinyan Ni and Zhaomei Shi and Jun Zhong and Ziqi Liang and Xiaoyu Fu and Hongqing Tu and Wenzhi Sun and Shen, {Wei L.} and Ji Hu and Jiajun Yang",
note = "Funding Information: We sincerely thank the participants of this study for their cooperation. We also thank the following individuals: all members of the Shen and Hu Lab of the School of Life Science and Technology, ShanghaiTech University for valuable discussion, the Proteomics technology platform of the School of Life Science and Technology, ShanghaiTech University for mass spectrometric analysis, the staff members of the Animal Facility at the National Facility for Protein Science in Shanghai (NFPS), Zhangjiang Lab, China for providing technical support and assistance, and JZ, the member of Delta Omics Inc., United States for analyzing the mass spectrometry data. Funding. This study is funded by the Shanghai University of Medicine and Health Sciences Seed Fund National Project Cultivation Special Project (JY, SFP-18-20-14-006), the Shanghai Science and Technology Commission Western Medicine Guidance Project (JY, 19411971400), National Nature Science Foundation of China (WS, 31771169 and 91857104), Innovation Program of Shanghai Municipal Education Commission (WS). Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Xiao, Luo, Yang, Zeng, Shen, Ni, Shi, Zhong, Liang, Fu, Tu, Sun, Shen, Hu and Yang.",
year = "2020",
month = apr,
day = "7",
doi = "10.3389/fncel.2020.00048",
language = "English (US)",
volume = "14",
journal = "Frontiers in Cellular Neuroscience",
issn = "1662-5102",
publisher = "Frontiers Research Foundation",
}