Institutional Repository of Key Laboratory of Mental Health, CAS
Epigenetic Activation of ASCT2 in the Hippocampus Contributes to Depression-Like Behavior by Regulating D-Serine in Mice | |
Wang, Jiesi1,2,3; Zhang, Ke2,3; Chen, Xiaojuan2,3; Liu, Xiaoqian2; Teng, Huajing1; Zhao, Mei2,3; Sun, Zhongsheng1,2,4; Mei Zhao; Zhongsheng Sun | |
第一作者 | Wang, Jiesi |
通讯作者邮箱 | zhaomei@psych.ac.cn ; sunzs@mail.biols.ac.cn |
心理所单位排序 | 2 |
摘要 | The roles of D-serine in depression are raised concerned recently as an intrinsic co-agonist for the NMDA receptor. However, the mechanisms underlying its regulation are not fully elucidated. ASCT2 is a Na+-dependent D-serine transporter. We found that decreased D-serine and increased hippocampal ASCT2 levels correlated with chronic social defeat stress (CSDS) in mice. Lentivirus-mediated shRNA-mediated knockdown of ASCT2 and the administration of exogenous D-serine in the hippocampus alleviated CSDS-induced social avoidance and immobility. In vivo and in vitro experiments revealed that upregulation of ASCT2 expression in CSDS was regulated through histone hyper-acetylation, not DNA methylation in its promoter region. Immunohistochemistry demonstrated the co-localization of ASCT2 and D-serine. Uptake of D-serine by ASCT2 was demonstrated by in vivo and in vitro experiments. Our results indicate that CSDS induces ASCT2 expression through epigenetic activation and decreases hippocampal D-serine levels, leading to social avoidance, and immobility. Thus, targeting D-serine transport represents an attractive new strategy for treating depression. |
关键词 | ASCT2 SLC1A5 D-serine depression chronic social defeat stress mouse |
2017-05-09 | |
DOI | 10.3389/fnmol.2017.00139 |
发表期刊 | FRONTIERS IN MOLECULAR NEUROSCIENCE |
ISSN | 1662-5099 |
卷号 | 10期号:0页码:1-13 |
收录类别 | SCI |
WOS关键词 | METHYL-D-ASPARTATE ; LONG-TERM POTENTIATION ; SOCIAL DEFEAT STRESS ; NUCLEUS-ACCUMBENS ; PSYCHIATRIC-DISORDERS ; IMIPRAMINE TREATMENT ; CHROMATIN REGULATION ; RECEPTOR-ACTIVITY ; DNA METHYLATION ; MOOD DISORDERS |
WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
WOS研究方向 | Neurosciences & Neurology |
WOS类目 | Neurosciences |
WOS记录号 | WOS:000401424100001 |
Q分类 | Q1 |
资助机构 | Key Project of the National 12th Five-Year Research Program of China(2012BAI03B02) ; National Health and Family Planning Commission of China(201302002) ; AstraZeneca Innovation Centre in China, and the International S&T Cooperation Program of China(2011DFA30670) |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.psych.ac.cn/handle/311026/21474 |
专题 | 中国科学院心理健康重点实验室 |
通讯作者 | Mei Zhao; Zhongsheng Sun |
作者单位 | 1.Chinese Acad Sci, Beijing Inst Life Sci, Beijing, Peoples R China 2.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Wenzhou Med Coll, Inst Genom Med, Wenzhou, Peoples R China |
第一作者单位 | 中国科学院心理健康重点实验室 |
推荐引用方式 GB/T 7714 | Wang, Jiesi,Zhang, Ke,Chen, Xiaojuan,et al. Epigenetic Activation of ASCT2 in the Hippocampus Contributes to Depression-Like Behavior by Regulating D-Serine in Mice[J]. FRONTIERS IN MOLECULAR NEUROSCIENCE,2017,10(0):1-13. |
APA | Wang, Jiesi.,Zhang, Ke.,Chen, Xiaojuan.,Liu, Xiaoqian.,Teng, Huajing.,...&Zhongsheng Sun.(2017).Epigenetic Activation of ASCT2 in the Hippocampus Contributes to Depression-Like Behavior by Regulating D-Serine in Mice.FRONTIERS IN MOLECULAR NEUROSCIENCE,10(0),1-13. |
MLA | Wang, Jiesi,et al."Epigenetic Activation of ASCT2 in the Hippocampus Contributes to Depression-Like Behavior by Regulating D-Serine in Mice".FRONTIERS IN MOLECULAR NEUROSCIENCE 10.0(2017):1-13. |
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Epigenetic Activatio(3049KB) | 期刊论文 | 出版稿 | 限制开放 | CC BY-NC-SA | 请求全文 |
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