Glycine exerts dual roles in ischemic injury through distinct mechanisms.
OBJECTIVE
We characterized the differential effects of glycine at different levels in the induction of postischemic long-term potentiation, as well as in the neuronal damage induced by focal ischemia.


METHODS
Whole-cell patch clamp recordings were obtained from rat hippocampal slice preparations. In vitro ischemia and postischemic long-term potentiation were induced by oxygen and glucose deprivation. In vivo ischemia was induced by transient middle cerebral artery occlusion.


RESULTS
In both in vitro and in vivo ischemia models, glycine at low level exerts deleterious effects in postischemic long-term potentiation and ischemic neuronal injury by modulation of the N-methyl-d-aspartate receptor coagonist site; whereas glycine at high level exerts neuroprotective effects by activation of glycine receptor and subsequent differential regulation of N-methyl-d-aspartate receptor subunit components.


CONCLUSIONS
Our results provide a molecular basis for the dual roles of glycine in ischemic injury through distinct mechanisms, and they suggest that glycine receptors could be a potential target for clinical treatment of stroke.
Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Wen
W
Yao
Fang
F
Ji
Zheng
Z
Chen
Nan
N
Zhang
Si-Qiang
SQ
Ren
Xiao-Yan
XY
Zhang
Su-Yi
SY
Liu
Wei
W
Lu
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000172:deficiency; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology*; D006624:Hippocampus / Q000473:pathology; D002534:Hypoxia, Brain / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013238:Stereotaxic Techniques; D014780:Viruses / Q000235:genetics
D015763:2-Amino-5-phosphonovalerate; D005947:Glucose; D005998:Glycine; D011810:Quinoxalines; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline