Increased concentrations of both NMDA receptor co-agonists D-serine and glycine in global ischemia
| Autor: | Leo W. J. Klomp, Ruud Berger, Sabine A. Fuchs, Martina M.J. de Barse, Martin W. Roeleveld, Cacha M.P.C.D. Peeters-Scholte, Tom J. de Koning |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Swine
Clinical Biochemistry Excitotoxicity medicine.disease_cause Biochemistry Serine Cerebrospinal fluid Ischemia Receptors Hypoxia Non-U.S. Gov't Neurons Asphyxia Neonatorum Respiratory Distress Syndrome Tumor Research Support Non-U.S. Gov't Glutamate receptor Brain Perinatal asphyxia d-Serine Anesthesia Hypoxia-Ischemia Brain NMDA receptor Original Article medicine.symptom Glutamate N-Methyl-D-Aspartate medicine.medical_specialty Glycine Biology Research Support Receptors N-Methyl-D-Aspartate Cell Line Internal medicine Cell Line Tumor Hypoxia-Ischemia medicine Journal Article Animals Humans Respiratory Distress Syndrome Newborn Organic Chemistry Infant Newborn Infant Hypoxia (medical) medicine.disease Newborn Rats Endocrinology nervous system Animals Newborn Reperfusion |
| Zdroj: | Amino Acids Amino Acids, 43(1), 355-363. SPRINGER WIEN |
| ISSN: | 1438-2199 0939-4451 |
| DOI: | 10.1007/s00726-011-1086-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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