TY - CHAP
T1 - D-serine influences synaptogenesis in a P19 cell model
AU - Fuchs, S.A.
AU - Roeleveld, M.W.
AU - Klomp, L.W.J.
AU - Berger, R.
AU - de Koning, T.J.
PY - 2012/1/1
Y1 - 2012/1/1
N2 - 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.
AB - 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.
KW - Central nervous system development
KW - Glial fibrillary acidic protein
KW - Neuronal circuitry
KW - NMDAr activation
KW - Serine racemase
UR - http://www.scopus.com/inward/record.url?scp=85017039613&partnerID=8YFLogxK
U2 - 10.1007/8904_2011_116
DO - 10.1007/8904_2011_116
M3 - Chapter
VL - 6
T3 - JIMD Reports
SP - 47
EP - 53
BT - JIMD Reports
PB - Springer
ER -