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Glycine bidirectionally regulates ischemic tolerance via different mechanisms including NR2A‐dependent CREB phosphorylation
Authors:Zheng Chen  Bin Hu  Fuzhou Wang  Linlin Du  Baosheng Huang  Lixin Li  Jia Qi  Xiang Wang
Institution:1. Division of Vascular Surgery, East Hospital, Tongji University School of Medicine, Shanghai, China;2. Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, China;3. Laboratory of Brain Diseases, College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, China;4. Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou, Jiangsu, China;5. Department of Anesthesiology, Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China;6. Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China
Abstract:The exact effect of glycine pre‐treatment on brain ischemic tolerance (IT) remains quite controversial. The objective of this study was to investigate the potential effects of glycine on IT. We used rat models of both in vitro ischemia (oxygen and glucose deprivation) and in vivo ischemia (transient middle cerebral artery occlusion). Low doses of glycine (L‐Gly) significantly decreased hippocampal ischemic LTP (i‐LTP), infarct volume, and neurological deficit scores which were administered before ischemia was induced in rats, whereas high doses of glycine exerted deteriorative effects under the same condition. These findings suggested that exogenous glycine may induce IT in a dose‐dependent manner. Furthermore, L‐Gly‐dependent neuronal protection was inversed by L689, a selective NMDAR glycine site antagonist both in vitro (abolished i‐LTP depression) and in vivo (increased infarct size reduction), but not glycine receptor (GlyR) inhibitor strychnine. Importantly, L‐Gly‐induced IT was achieved by NR2A‐dependent cAMP‐response element binding protein phosphorylation. These data imply that glycine pre‐treatment may represent a novel strategy for inducing IT based on synaptic NMDAR‐dependent neuronal transmission.
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Keywords:glycine  iLTP  ischemic tolerance  NMDAR  tMCAO
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