Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Stroke. 2012 Aug;43(8):2212-20. doi: 10.1161/STROKEAHA.111.645994. Epub 2012 Jun 12.
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.
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.
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.
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.
本研究旨在探讨甘氨酸在诱导缺血后长期增强（postischemic long-term potentiation，LTP）以及局灶性缺血引起的神经元损伤中的不同作用及其作用机制。
采用全细胞膜片钳记录技术，对大鼠海马脑片进行检测。体外缺血和缺血后 LTP 由缺氧和葡萄糖剥夺诱导，体内缺血由短暂性大脑中动脉闭塞诱导。
在体外和体内缺血模型中，低水平的甘氨酸通过调节 N-甲基-D-天冬氨酸（N-methyl-D-aspartate，NMDA）受体共激动剂结合位点对缺血后 LTP 和缺血性神经元损伤产生有害作用；而高水平的甘氨酸通过甘氨酸受体的激活以及随后对 NMDA 受体亚单位成分的差异调节发挥神经保护作用。
本研究结果为甘氨酸通过不同机制在缺血损伤中的双重作用提供了分子基础，表明甘氨酸受体可能成为治疗中风的潜在靶点。
