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Astrocytic <scp>d</scp>‐amino acid oxidase degrades <scp>d</scp>‐serine in the hindbrain

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

2022FEBS Letters19 citationsDOI

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.

Topics & Concepts

ForebrainHindbrainSerineGlutamate receptorAmino acidAstrocyteBiochemistryReceptorD-amino acid oxidaseConditional gene knockoutBiologyChemistryNeuroscienceCentral nervous systemOxidase testPhosphorylationEnzymeGenePhenotypeAmino Acid Enzymes and MetabolismNeuroscience and Neuropharmacology ResearchPhotoreceptor and optogenetics research
Astrocytic <scp>d</scp>‐amino acid oxidase degrades <scp>d</scp>‐serine in the hindbrain | Litcius