Publication

Increased concentrations of both NMDA receptor co-agonists D-serine and glycine in global ischemia: A potential novel treatment target for perinatal asphyxia

Fuchs, S. A., Peeters-Scholte, C. M. P. C. D., de Barse, M. M. J., Roeleveld, M. W., Klomp, L. W. J., Berger, R. & de Koning, T. J., Jul-2012, In : Amino Acids. 43, 1, p. 355-363 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Fuchs, S. A., Peeters-Scholte, C. M. P. C. D., de Barse, M. M. J., Roeleveld, M. W., Klomp, L. W. J., Berger, R., & de Koning, T. J. (2012). Increased concentrations of both NMDA receptor co-agonists D-serine and glycine in global ischemia: A potential novel treatment target for perinatal asphyxia. Amino Acids, 43(1), 355-363. https://doi.org/10.1007/s00726-011-1086-9

Author

Fuchs, Sabine A ; Peeters-Scholte, Cacha M P C D ; de Barse, Martina M J ; Roeleveld, Martin W ; Klomp, Leo W J ; Berger, Ruud ; de Koning, Tom J. / Increased concentrations of both NMDA receptor co-agonists D-serine and glycine in global ischemia : A potential novel treatment target for perinatal asphyxia. In: Amino Acids. 2012 ; Vol. 43, No. 1. pp. 355-363.

Harvard

Fuchs, SA, Peeters-Scholte, CMPCD, de Barse, MMJ, Roeleveld, MW, Klomp, LWJ, Berger, R & de Koning, TJ 2012, 'Increased concentrations of both NMDA receptor co-agonists D-serine and glycine in global ischemia: A potential novel treatment target for perinatal asphyxia', Amino Acids, vol. 43, no. 1, pp. 355-363. https://doi.org/10.1007/s00726-011-1086-9

Standard

Increased concentrations of both NMDA receptor co-agonists D-serine and glycine in global ischemia : A potential novel treatment target for perinatal asphyxia. / Fuchs, Sabine A; Peeters-Scholte, Cacha M P C D; de Barse, Martina M J; Roeleveld, Martin W; Klomp, Leo W J; Berger, Ruud; de Koning, Tom J.

In: Amino Acids, Vol. 43, No. 1, 07.2012, p. 355-363.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Fuchs SA, Peeters-Scholte CMPCD, de Barse MMJ, Roeleveld MW, Klomp LWJ, Berger R et al. Increased concentrations of both NMDA receptor co-agonists D-serine and glycine in global ischemia: A potential novel treatment target for perinatal asphyxia. Amino Acids. 2012 Jul;43(1):355-363. https://doi.org/10.1007/s00726-011-1086-9


BibTeX

@article{9dc1f54e60794e35993befe6e4f42328,
title = "Increased concentrations of both NMDA receptor co-agonists D-serine and glycine in global ischemia: A potential novel treatment target for perinatal asphyxia",
abstract = "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.",
keywords = "Animals, Animals, Newborn, Asphyxia Neonatorum, Cell Line, Tumor, Glycine, Humans, Hypoxia, Hypoxia-Ischemia, Brain, Infant, Newborn, Neurons, Rats, Receptors, N-Methyl-D-Aspartate, Reperfusion, Respiratory Distress Syndrome, Newborn, Serine, Swine, Journal Article, Research Support, Non-U.S. Gov't",
author = "Fuchs, {Sabine A} and Peeters-Scholte, {Cacha M P C D} and {de Barse}, {Martina M J} and Roeleveld, {Martin W} and Klomp, {Leo W J} and Ruud Berger and {de Koning}, {Tom J}",
year = "2012",
month = jul,
doi = "10.1007/s00726-011-1086-9",
language = "English",
volume = "43",
pages = "355--363",
journal = "Amino Acids",
issn = "0939-4451",
publisher = "SPRINGER WIEN",
number = "1",

}

RIS

TY - JOUR

T1 - Increased concentrations of both NMDA receptor co-agonists D-serine and glycine in global ischemia

T2 - A potential novel treatment target for perinatal asphyxia

AU - Fuchs, Sabine A

AU - Peeters-Scholte, Cacha M P C D

AU - de Barse, Martina M J

AU - Roeleveld, Martin W

AU - Klomp, Leo W J

AU - Berger, Ruud

AU - de Koning, Tom J

PY - 2012/7

Y1 - 2012/7

N2 - 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.

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.

KW - Animals

KW - Animals, Newborn

KW - Asphyxia Neonatorum

KW - Cell Line, Tumor

KW - Glycine

KW - Humans

KW - Hypoxia

KW - Hypoxia-Ischemia, Brain

KW - Infant, Newborn

KW - Neurons

KW - Rats

KW - Receptors, N-Methyl-D-Aspartate

KW - Reperfusion

KW - Respiratory Distress Syndrome, Newborn

KW - Serine

KW - Swine

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1007/s00726-011-1086-9

DO - 10.1007/s00726-011-1086-9

M3 - Article

C2 - 21947661

VL - 43

SP - 355

EP - 363

JO - Amino Acids

JF - Amino Acids

SN - 0939-4451

IS - 1

ER -

ID: 49236811