D-serine influences synaptogenesis in a P19 cell model
(2012) In JIMD Reports 6. p.47-53- 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... (More)
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.
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- author
- Fuchs, Sabine A. ; Roeleveld, Martin W. ; Klomp, Leo W.J. ; Berger, Ruud and de Koning, Tom J. LU
- publishing date
- 2012-01-01
- type
- Chapter in Book/Report/Conference proceeding
- publication status
- published
- subject
- keywords
- Central nervous system development, Glial fibrillary acidic protein, Neuronal circuitry, NMDAr activation, Serine racemase
- host publication
- JIMD Reports
- series title
- JIMD Reports
- volume
- 6
- pages
- 7 pages
- publisher
- Springer Gabler
- external identifiers
-
- scopus:85017039613
- ISSN
- 2192-8312
- 2192-8304
- DOI
- 10.1007/8904_2011_116
- language
- English
- LU publication?
- no
- id
- 830f7011-e1f0-41bd-a827-2b168a0f984a
- date added to LUP
- 2020-02-26 10:14:27
- date last changed
- 2024-01-02 06:30:21
@inbook{830f7011-e1f0-41bd-a827-2b168a0f984a,
abstract = {{<p>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.</p>}},
author = {{Fuchs, Sabine A. and Roeleveld, Martin W. and Klomp, Leo W.J. and Berger, Ruud and de Koning, Tom J.}},
booktitle = {{JIMD Reports}},
issn = {{2192-8312}},
keywords = {{Central nervous system development; Glial fibrillary acidic protein; Neuronal circuitry; NMDAr activation; Serine racemase}},
language = {{eng}},
month = {{01}},
pages = {{47--53}},
publisher = {{Springer Gabler}},
series = {{JIMD Reports}},
title = {{D-serine influences synaptogenesis in a P19 cell model}},
url = {{http://dx.doi.org/10.1007/8904_2011_116}},
doi = {{10.1007/8904_2011_116}},
volume = {{6}},
year = {{2012}},
}