Increased concentrations of both NMDA receptor co-agonists d-serine and glycine in global ischemia : A potential novel treatment target for perinatal asphyxia
(2012) In Amino Acids 43(1). p.355-363- 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... (More)
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.
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- 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 and De Koning, Tom J. LU
- publishing date
- 2012-07-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- d-Serine, Glutamate, Ischemia, NMDA receptor, Perinatal asphyxia
- in
- Amino Acids
- volume
- 43
- issue
- 1
- pages
- 9 pages
- publisher
- Springer
- external identifiers
-
- pmid:21947661
- scopus:84862753773
- ISSN
- 0939-4451
- DOI
- 10.1007/s00726-011-1086-9
- language
- English
- LU publication?
- no
- id
- 518513f9-87d8-41a8-abaf-3e63e1927b68
- date added to LUP
- 2020-02-26 10:17:05
- date last changed
- 2024-04-03 03:41:45
@article{518513f9-87d8-41a8-abaf-3e63e1927b68,
abstract = {{<p>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.</p>}},
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 Berger, Ruud and De Koning, Tom J.}},
issn = {{0939-4451}},
keywords = {{d-Serine; Glutamate; Ischemia; NMDA receptor; Perinatal asphyxia}},
language = {{eng}},
month = {{07}},
number = {{1}},
pages = {{355--363}},
publisher = {{Springer}},
series = {{Amino Acids}},
title = {{Increased concentrations of both NMDA receptor co-agonists d-serine and glycine in global ischemia : A potential novel treatment target for perinatal asphyxia}},
url = {{http://dx.doi.org/10.1007/s00726-011-1086-9}},
doi = {{10.1007/s00726-011-1086-9}},
volume = {{43}},
year = {{2012}},
}