Astrocytic D-amino acid oxidase degrades D-serine in the hindbrain

被引：8

作者：

Gonda, Yusuke ^{[1
,2
]}

Ishii, Chiharu ^{[3
]}

Mita, Masashi ^{[4
]}

Nishizaki, Naoto ^{[5
]}

Ohtomo, Yoshiyuki ^{[6
]}

Hamase, Kenji ^{[3
]}

Shimizu, Toshiaki ^{[2
]}

Sasabe, Jumpei ^{[1
]}

机构：

[1] Keio Univ, Sch Med, Dept Pharmacol, Tokyo 1608582, Japan

[2] Juntendo Univ, Grad Sch Med, Dept Pediat & Adolescent Med, Tokyo, Japan

[3] Kyushu Univ, Grad Sch Pharmaceut Sci, Fukuoka, Japan

[4] KAGAMI Inc, Ibaraki, Japan

[5] Juntendo Univ, Urayasu Hosp, Dept Pediat, Chiba, Japan

[6] Juntendo Univ, Nerima Hosp, Dept Pediat, Tokyo, Japan

来源：

FEBS LETTERS | 2022年 / 596卷 / 22期

关键词：

chirality; D-alanine; D-amino acid oxidase; D-serine; AMYOTROPHIC-LATERAL-SCLEROSIS; D-ALANINE; D-ASPARTATE; GLYCINE SITE; RAT-BRAIN; RACEMASE; MICE; NMDA; SCHIZOPHRENIA; LOCALIZATION;

D O I：

10.1002/1873-3468.14417

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

D-Serine modulates excitatory neurotransmission by binding to N-methyl-D-aspartate glutamate receptors. D-Amino acid oxidase (DAO) degrades D-amino acids, such as D-serine, in the central nervous system, and is associated with neurological and psychiatric disorders. However, cell types that express brain DAO remain controversial, and whether brain DAO influences systemic D-amino acids in addition to brain D-serine remains unclear. Here, we created astrocyte-specific DAO-conditional knockout mice. Knockout in glial fibrillary acidic protein-positive cells eliminated DAO expression in the hindbrain and increased D-serine levels significantly in the cerebellum. Brain DAO did not influence levels of D-amino acids in the forebrain or periphery. These results show that astrocytic DAO regulates D-serine specifically in the hindbrain.

引用

页码：2889 / 2897

页数：9

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