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

Yusuke Gonda, Chiharu Ishii, Masashi Mita, Naoto Nishizaki, Yoshiyuki Ohtomo, Kenji Hamase, Toshiaki Shimizu, Jumpei Sasabe

Research output: Contribution to journalLetterpeer-review

Abstract

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.

Original languageEnglish
JournalFEBS Letters
DOIs
Publication statusAccepted/In press - 2022

Keywords

  • chirality
  • d-alanine
  • d-amino acid oxidase
  • d-serine

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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