title: D-serine influences synaptogenesis in a p19 cell model.
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.
authors: Department of Metabolic and Endocrine Diseases/Department of Biomedical Genetics, University Medical Center Utrecht, 85090, 3508 AB, Utrecht, The Netherlands, S.Fuchs@umcutrecht.nl.
authors: Sabine A
authors: SA
authors: Fuchs
authors: Martin W
authors: MW
authors: Roeleveld
authors: Leo W J
authors: LW
authors: Klomp
authors: Ruud
authors: R
authors: Berger
authors: Tom J
authors: TJ
authors: de Koning