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Striatal N-Acetylaspartate Synthetase Shati/Nat8l Regulates Depression-Like Behaviors via mGluR3-Mediated Serotonergic Suppression in Mice
http://hdl.handle.net/10110/00018213
http://hdl.handle.net/10110/00018213a2416dbe-2fb3-4707-b02a-aaab4d11ce69
名前 / ファイル | ライセンス | アクション |
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IJN_20(12)_1027to1035_Miyamoto (1.0 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2018-02-25 | |||||
タイトル | ||||||
タイトル | Striatal N-Acetylaspartate Synthetase Shati/Nat8l Regulates Depression-Like Behaviors via mGluR3-Mediated Serotonergic Suppression in Mice | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Shati/Nat8l | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | behavioral despair | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | social withdrawal | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | mGluR3 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | serotonin | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Miyamoto, Yoshiaki
× Miyamoto, Yoshiaki× Iegaki, Noriyuki× Fu, equan× Ishikawa, Yudai× Sumi, Kazuyuki× Azuma, Sota× Uno, Kyosuke× Muramatsu, Shin-ichi× Nitta, Atsumi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Background: Several clinical studies have suggested that N-acetylaspartate and N-acetylaspartylglutamate levels in the human brain are associated with various psychiatric disorders, including major depressive disorder. We have previously identified Shati/Nat8l, an N-acetyltransferase, in the brain using an animal model of psychosis. Shati/Nat8l synthesizes N-acetylaspartate from L-aspartate and acetyl-coenzyme A. Further, N-acetylaspartate is converted into N-acetylaspartylglutamate, a neurotransmitter for metabotropic glutamate receptor 3. Methods: Because Shati/Nat8l mRNA levels were increased in the dorsal striatum of mice following the exposure to forced swimming stress, Shati/Nat8l was overexpressed in mice by the microinjection of adeno-associated virus vectors containing Shati/Nat8l gene into the dorsal striatum (dS-Shati/Nat8l mice). The dS-Shati/Nat8l mice were further assessed using behavioral and neurochemical tests. Results: The dS-Shati/Nat8l mice exhibited behavioral despair in the forced swimming and tail suspension tests and social withdrawal in the 3-chamber social interaction test. These depression-like behaviors were attenuated by the administration of a metabotropic glutamate receptor 2/3 antagonist and a selective serotonin reuptake inhibitor. Furthermore, the metabolism of N-acetylaspartate to N-acetylaspartylglutamate was decreased in the dorsal striatum of the dS-Shati/Nat8l mice. This finding corresponded with the increased expression of glutamate carboxypeptidase II, an enzyme that metabolizes Nacetylaspartylglutamate present in the extracellular space. Extracellular serotonin levels were lower in the dorsal striatum of the dS-Shati/Nat8l and normal mice that were repeatedly administered a selective glutamate carboxypeptidase II inhibitor. Conclusions: Our findings indicate that the striatal expression of N-acetylaspartate synthetase Shati/Nat8l plays a role in major depressive disorder via the metabotropic glutamate receptor 3-mediated functional control of the serotonergic neuronal system. |
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引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | International Journal of Neuropsychopharmacology (2017) 20(12): 1027–1035 | |||||
書誌情報 |
International Journal of Neuropsychopharmacology 巻 20, 号 12, p. 1027-1035, 発行日 2017-08-31 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1461-1457 | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1469-5111 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | info:doi/10.1093/ijnp/pyx078 | |||||
権利 | ||||||
権利情報 | © The Author(s) 2017. Published by Oxford University Press on behalf of CINP. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
出版者 | ||||||
出版者 | Oxford University Press | |||||
資源タイプ(DSpace) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Article |