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Neurogenesis Using P19 Embryonal Carcinoma Cells
Published on: April 27, 2019
D-serine influences synaptogenesis in a p19 cell model
Sabine A Fuchs1, Martin W Roeleveld, Leo W J Klomp
1Department of Metabolic and Endocrine Diseases/Department of Biomedical Genetics, University Medical Center Utrecht, 85090, 3508 AB, Utrecht, The Netherlands, S.Fuchs@umcutrecht.nl.
JIMD Reports
|February 23, 2013
Summary
D-serine, an NMDA-receptor co-agonist, is crucial for central nervous system development. Its deficiency is linked to neurological and psychiatric disorders, impacting neuronal circuitry and synaptogenesis.
Area of Science:
- Neuroscience
- Developmental Biology
- Biochemistry
Background:
- D-serine acts as a crucial co-agonist for NMDA receptors.
- Its role in central nervous system (CNS) development is under investigation.
- Neuronal and glial differentiation models are essential for studying developmental processes.
Purpose of the Study:
- To investigate the role of D-serine in neuronal and glial differentiation using rat P19 cells.
- To examine the expression and activity of serine racemase during differentiation.
- To determine the impact of D-serine modulation on synaptogenesis and neuronal connectivity.
Main Methods:
- Utilized rat P19 cells as a model for neuronal and glial differentiation.
- Analyzed serine racemase expression and activity.
- Measured extracellular D-serine concentrations.
- Investigated the effects of serine racemase antagonism and NMDA receptor blockade on cellular processes.
Main Results:
- Serine racemase expression was induced upon P19 cell differentiation.
- Extracellular D-serine levels increased during differentiation, modulated by serine racemase activity.
- Inhibiting D-serine synthesis or NMDA receptor binding enhanced synaptophysin expression and intercellular connections.
Conclusions:
- NMDA receptor activation by D-serine, synthesized by serine racemase, plays a role in shaping synaptogenesis and neuronal circuitry during CNS development.
- D-serine deficiency may underlie neurological phenotypes in serine deficiency disorders.
- This study suggests a potential pathophysiological mechanism for D-serine deficiency in psychiatric disorders.
