PMID- 21947661
OWN - NLM
STAT- MEDLINE
DCOM- 20121214
LR  - 20211020
IS  - 1438-2199 (Electronic)
IS  - 0939-4451 (Print)
IS  - 0939-4451 (Linking)
VI  - 43
IP  - 1
DP  - 2012 Jul
TI  - Increased concentrations of both NMDA receptor co-agonists D-serine and glycine 
      in global ischemia: a potential novel treatment target for perinatal asphyxia.
PG  - 355-63
LID - 10.1007/s00726-011-1086-9 [doi]
AB  - Worldwide, perinatal asphyxia is an important cause of morbidity and mortality 
      among term-born children. Overactivation of the N-methyl-D-aspartate receptor 
      (NMDAr) plays a central role in the pathogenesis of cerebral hypoxia-ischemia, 
      but the role of both endogenous NMDAr co-agonists D-serine and glycine remains 
      largely elusive. We investigated D-serine and glycine concentration changes in 
      rat glioma cells, subjected to oxygen and glucose deprivation (OGD) and CSF from 
      piglets exposed to hypoxia-ischemia by occlusion of both carotid arteries and 
      hypoxia. We illustrated these findings with analyses of cerebrospinal fluid (CSF) 
      from human newborns affected by perinatal asphyxia. Extracellular concentrations 
      of glycine and D-serine were markedly increased in rat glioma cells exposed to 
      OGD, presumably through increased synthesis from L-serine. Upon reperfusion 
      glycine concentrations normalized and D-serine concentrations were significantly 
      lowered. The in vivo studies corroborated the finding of initially elevated and 
      then normalizing concentrations of glycine and decreased D-serine concentrations 
      upon reperfusion These significant increases of both endogenous NMDAr co-agonists 
      in combination with elevated glutamate concentrations, as induced by global 
      cerebral ischemia, are bound to lead to massive NMDAr activation, excitotoxicity 
      and neuronal damage. Influencing these NMDAr co-agonist concentrations provides 
      an interesting treatment target for this common, devastating and currently poorly 
      treatable condition.
FAU - Fuchs, Sabine A
AU  - Fuchs SA
AD  - Department of Metabolic and Endocrine Diseases, University Medical Center 
      Utrecht, Postbox 85090, 3508 AB, Utrecht, The Netherlands. S.Fuchs@umcutrecht.nl
FAU - Peeters-Scholte, Cacha M P C D
AU  - Peeters-Scholte CM
FAU - de Barse, Martina M J
AU  - de Barse MM
FAU - Roeleveld, Martin W
AU  - Roeleveld MW
FAU - Klomp, Leo W J
AU  - Klomp LW
FAU - Berger, Ruud
AU  - Berger R
FAU - de Koning, Tom J
AU  - de Koning TJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110923
PL  - Austria
TA  - Amino Acids
JT  - Amino acids
JID - 9200312
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 452VLY9402 (Serine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Asphyxia Neonatorum/*cerebrospinal fluid/metabolism
MH  - Cell Line, Tumor
MH  - Glycine/*analysis
MH  - Humans
MH  - Hypoxia
MH  - Hypoxia-Ischemia, Brain/cerebrospinal fluid/*metabolism
MH  - Infant, Newborn
MH  - Neurons/metabolism
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/agonists/antagonists & inhibitors/*metabolism
MH  - *Reperfusion
MH  - Respiratory Distress Syndrome, Newborn/cerebrospinal fluid/metabolism
MH  - Serine/*analysis
MH  - Swine
PMC - PMC3374112
EDAT- 2011/09/29 06:00
MHDA- 2012/12/15 06:00
PMCR- 2011/09/23
CRDT- 2011/09/28 06:00
PHST- 2011/04/28 00:00 [received]
PHST- 2011/09/13 00:00 [accepted]
PHST- 2011/09/28 06:00 [entrez]
PHST- 2011/09/29 06:00 [pubmed]
PHST- 2012/12/15 06:00 [medline]
PHST- 2011/09/23 00:00 [pmc-release]
AID - 1086 [pii]
AID - 10.1007/s00726-011-1086-9 [doi]
PST - ppublish
SO  - Amino Acids. 2012 Jul;43(1):355-63. doi: 10.1007/s00726-011-1086-9. Epub 2011 Sep 
      23.