D-serine influences synaptogenesis in a p19 cell model

Sabine A Fuchs, Martin W Roeleveld, Leo W J Klomp, Ruud Berger, Tom J de Koning

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

4 Citations (Scopus)

Abstract

Recently, D-serine has been identified as an important NMDA-receptor co-agonist, which might play a role in central nervous system development. We investigated this by studying rat P19 cells, an established model for neuronal and glial differentiation. Our results show that (1) the D-serine synthesizing enzyme serine racemase was expressed upon differentiation, (2) extracellular D-serine concentrations increased upon differentiation, which was inhibited by serine racemase antagonism, and (3) inhibition of D-serine synthesis or prevention of D-serine binding to the NMDA-receptor increased synaptophysin expression and intercellular connections, supporting a role for NMDA-receptor activation by D-serine, synthesized by serine racemase, in shaping synaptogenesis and neuronal circuitry during central nervous system development. In conjunction with recent evidence from literature, we therefore suggest that D-serine deficiency might be responsible for the severe neurological phenotype seen in patients with serine deficiency disorders. In addition, this may provide a pathophysiological mechanism for a role of D-serine deficiency in psychiatric disorders.

Original languageEnglish
Title of host publicationJIMD Reports - Case and Research Reports, 2012/3
EditorsSociety for the Study of Inborn Errors of Metabolism
PublisherSpringer-Verlag Berlin Heidelberg
Pages47-53
Number of pages7
Volume6
ISBN (Electronic)978-3-642-28129-7
ISBN (Print)978-3-642-28128-0
DOIs
Publication statusPublished - 2012
Externally publishedYes

Publication series

NameJournal of Inherited Metabolic Disorders
ISSN (Print)2192-8304

Cite this