N-METHYL-D-ASPARTATE RECEPTOR GLYCINE-BINDING SITE ANTAGONIST, SM-31900 PROTECTS AGAINST DELAYED NEURONAL DEATH AND REDUCES NEUROGENESIS INDUCED BY TRANSIENT GLOBAL ISCHEMIA IN RATS

「Abstract」The N-methyl-D-aspartate receptor (NMDAR) is known to play an important role in ischemic neuronal injury in the hippocampus, and also implicated in modulation of neurogenesis in the hippocampal dentate gyrus (DG). Recent evidence confirmed that amino acid neurotransmitter glycine acts as a coagonist in excitatory neurotransmission at NMDAR. The aim of this study is to investigate the role of glycine in ischemic injury and neurogenesis in the hippocampus in the rat global ischemia model. Global ischemia was induced with or without the treatment with NMDAR antagonist or NMDAR glycine site blocker. Neuronal injury was morphologically examined and neurogenesis was assessed by bromodeoxyuridine uptake. Global ischemia induced severe injury in the hippocampal CA1 neurons, but pharmacological antagonism of NMDAR or glycine site ameliorated the injury. Global ischemia enhanced neurogenesis in DG, but these pharmacological interventions resulted in attenuation of neurogenesis. These results suggest that glycine plays an important role in NMDAR-mediated neuronal injury and regulation of neurogenesis in the hippocampus.