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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
2017-05-09
Source PublicationFRONTIERS IN MOLECULAR NEUROSCIENCE
Correspondent Emailzhaomei@psych.ac.cn ; sunzs@mail.biols.ac.cn
ISSN1662-5099
SubtypeArticle
Volume10Issue:0Pages:1-13
Abstract

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.

KeywordASCT2 SLC1A5 D-serine depression chronic social defeat stress mouse
DOI10.3389/fnmol.2017.00139
Indexed BySCI
Language英语
Funding OrganizationKey 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)
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000401424100001
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS KeywordMETHYL-D-ASPARTATE ; LONG-TERM POTENTIATION ; SOCIAL DEFEAT STRESS ; NUCLEUS-ACCUMBENS ; PSYCHIATRIC-DISORDERS ; IMIPRAMINE TREATMENT ; CHROMATIN REGULATION ; RECEPTOR-ACTIVITY ; DNA METHYLATION ; MOOD DISORDERS
Citation statistics
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/21474
Collection中国科学院心理健康重点实验室
Corresponding AuthorMei Zhao; Zhongsheng Sun
Affiliation1.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
First Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
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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