Striatal N-Acetylaspartate Synthetase Shati/Nat8l Regulates Depression-Like Behaviors via mGluR3-Mediated Serotonergic Suppression in Mice.
Striatal N-Acetylaspartate Synthetase Shati/Nat8l Regulates Depression-Like Behaviors via mGluR3-Mediated Serotonergic Suppression in Mice.
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DOI：
10.1093/ijnp/pyx078
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发表时间：
2017-12-01
期刊：
影响因子：
--
通讯作者：
Nitta A
中科院分区：
文献类型：
--
作者：
Miyamoto Y;Iegaki N;Fu K;Ishikawa Y;Sumi K;Azuma S;Uno K;Muramatsu SI;Nitta A
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. 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. 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 N-acetylaspartylglutamate 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. 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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影响因子：
168.9
作者：
Kupfer, David J.;Frank, Ellen;Phillips, Mary L.
通讯作者：
Phillips, Mary L.
影响因子：
6.8
作者：
Aoki Y;Abe O;Yahata N;Kuwabara H;Natsubori T;Iwashiro N;Takano Y;Inoue H;Kawakubo Y;Gonoi W;Sasaki H;Murakami M;Katsura M;Nippashi Y;Takao H;Kunimatsu A;Matsuzaki H;Tsuchiya KJ;Kato N;Kasai K;Yamasue H
通讯作者：
Yamasue H
影响因子：
11
作者：
Kato, M.;Serretti, A.
通讯作者：
Serretti, A.
影响因子：
--
作者：
Michelsen, Kimmo A.;Schmitz, Christoph;Steinbusch, Harry W. M.
通讯作者：
Steinbusch, Harry W. M.
DOI：
10.1007/bf01181604
发表时间：
1995-06-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
MOFFETT, JR;NAMBOODIRI, MAA
通讯作者：
NAMBOODIRI, MAA