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

FEBS Lett. 2022 Nov;596(22):2889-2897. doi: 10.1002/1873-3468.14417. Epub 2022 Jun 14.

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.

Keywords: chirality; d-alanine; d-amino acid oxidase; d-serine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids
  • Animals
  • Astrocytes / metabolism
  • Cerebellum / metabolism
  • D-Amino-Acid Oxidase* / genetics
  • D-Amino-Acid Oxidase* / metabolism
  • Mice
  • Mice, Knockout
  • Serine* / metabolism

Substances

  • Serine
  • D-Amino-Acid Oxidase
  • Amino Acids