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

OnderzoeksoutputAcademicpeer review

4 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
TitelJIMD Reports - Case and Research Reports, 2012/3
RedacteurenSociety for the Study of Inborn Errors of Metabolism
UitgeverijSpringer-Verlag Berlin Heidelberg
Pagina's47-53
Aantal pagina's7
Volume6
ISBN van elektronische versie978-3-642-28129-7
ISBN van geprinte versie978-3-642-28128-0
DOI's
StatusPublished - 2012
Extern gepubliceerdJa

Publicatie series

NaamJournal of Inherited Metabolic Disorders
ISSN van geprinte versie2192-8304

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