A Brain Signaling Framework for Stress-Induced Depression and Ketamine Treatment Elucidated by Phosphoproteomics
Xiao, Yan1; Luo, Huoqing2,3,4; Yang, Wen Z.2,5,6; Zeng, Yeting1; Shen, Yinbo1; Ni, Xinyan2; Shi, Zhaomei2; Zhong, Jun7; Liang, Ziqi2; Fu, Xiaoyu2,3,4
2020-04-07
发表期刊FRONTIERS IN CELLULAR NEUROSCIENCE
ISSN1662-5102
EISSN1662-5102
卷号14
发表状态已发表
DOI10.3389/fncel.2020.00048
摘要

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.

关键词depression chronic unpredictable mild stress (CUMS) ketamine LC-MS MS phosphoproteomics brain signaling
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收录类别SCI ; SCIE
资助项目National Nature Science Foundation of China[31771169] ; National Nature Science Foundation of China[91857104]
WOS研究方向Neurosciences & Neurology
WOS类目Neurosciences
WOS记录号WOS:000529257000001
出版者FRONTIERS MEDIA SA
WOS关键词LONG-TERM DEPRESSION ; INTERMEDIATE CHAIN 1 ; KINASE-C-GAMMA ; SYNAPTIC PLASTICITY ; PREFRONTAL CORTEX ; MASS-SPECTROMETRY ; MAJOR DEPRESSION ; LATERAL HABENULA ; MILD STRESS ; PKC-GAMMA
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/119531
专题生命科学与技术学院_博士生
生命科学与技术学院_PI研究组_胡霁组
生命科学与技术学院_PI研究组_沈伟组
免疫化学研究所
生命科学与技术学院_公共科研平台_组学分析平台
生命科学与技术学院_硕士生
共同第一作者Luo, Huoqing
通讯作者Shen, Wei L.; Hu, Ji; Yang, Jiajun
作者单位1.Shanghai Jiao Tong Univ, Dept Neurol, Peoples Hosp 6, Shanghai, Peoples R China
2.Shanghaitech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
3.Chinese Acad Sci, Inst Neurosci, Shanghai Inst Biol Sci,State Key Lab Neurosci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai, Peoples R China
4.Univ Chinese Acad Sci, Beijing, Peoples R China
5.Shanghaitech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Organ Chem, CAS Key Lab Synthet Chem Nat Subst, Shanghai, Peoples R China
7.Delta Omics Inc, Baltimore, MD USA
8.Chinese Inst Brain Res, Beijing, Peoples R China
通讯作者单位生命科学与技术学院
推荐引用方式
GB/T 7714
Xiao, Yan,Luo, Huoqing,Yang, Wen Z.,et al. A Brain Signaling Framework for Stress-Induced Depression and Ketamine Treatment Elucidated by Phosphoproteomics[J]. FRONTIERS IN CELLULAR NEUROSCIENCE,2020,14.
APA Xiao, Yan.,Luo, Huoqing.,Yang, Wen Z..,Zeng, Yeting.,Shen, Yinbo.,...&Yang, Jiajun.(2020).A Brain Signaling Framework for Stress-Induced Depression and Ketamine Treatment Elucidated by Phosphoproteomics.FRONTIERS IN CELLULAR NEUROSCIENCE,14.
MLA Xiao, Yan,et al."A Brain Signaling Framework for Stress-Induced Depression and Ketamine Treatment Elucidated by Phosphoproteomics".FRONTIERS IN CELLULAR NEUROSCIENCE 14(2020).
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