Wang Wei-Ping, Iyo Abiye H, Miguel-Hidalgo Javier, Regunathan Soundar, Zhu Meng-Yang
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS 39216, USA.
Brain Res. 2006 Apr 21;1084(1):210-6. doi: 10.1016/j.brainres.2006.02.024. Epub 2006 Mar 20.
Agmatine is a polyamine and has been considered as a novel neurotransmitter or neuromodulator in the central nervous system. In the present study, the neuroprotective effect of agmatine against cell damage caused by N-methyl-D-aspartate (NMDA) and glutamate was investigated in cultured rat hippocampal neurons. Lactate dehydrogenase (LDH) activity assay, beta-tubulin III immunocytochemical staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL) assay were conducted to detect cell damage. Exposure of 12-day neuronal cultures of rat hippocampus to NMDA or glutamate for 1 h caused a concentration-dependent neurotoxicity, as indicated by the significant increase in released LDH activities. Addition of 100 microM agmatine into media ablated the neurotoxicity induced by NMDA or glutamate, an effect also produced by the specific NMDA receptor antagonist dizocilpine hydrogen maleate (MK801). Arcaine, an analog of agmatine with similar structure as agmatine, fully prevented the NMDA- or glutamate-induced neuronal damage. Spermine and putrescine, the endogenous polyamine and metabolic products of agmatine without the guanidine moiety of agmatine, failed to show this effect, indicating a structural relevance for this neuroprotection. Immunocytochemical staining and TUNEL assay confirmed the findings in the LDH measurement. That is, agmatine and MK801 markedly attenuated NMDA-induced neuronal death and significantly reduced TUNEL-positive cell numbers induced by exposure of cultured hippocampal neurons to NMDA. Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from NMDA- or glutamate-induced excitotoxicity, through a possible blockade of the NMDA receptor channels or a potential anti-apoptotic property.
胍丁胺是一种多胺，被认为是中枢神经系统中的一种新型神经递质或神经调节剂。在本研究中，在培养的大鼠海马神经元中研究了胍丁胺对由N-甲基-D-天冬氨酸（NMDA）和谷氨酸引起的细胞损伤的神经保护作用。进行乳酸脱氢酶（LDH）活性测定、β-微管蛋白III免疫细胞化学染色和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸（dUTP）缺口末端标记（TUNEL）测定以检测细胞损伤。将大鼠海马12天的神经元培养物暴露于NMDA或谷氨酸1小时会导致浓度依赖性神经毒性，这表现为释放的LDH活性显著增加。向培养基中添加100 microM胍丁胺消除了由NMDA或谷氨酸诱导的神经毒性，特异性NMDA受体拮抗剂马来酸氢氯氮平（MK801）也产生了这种效果。精胺和腐胺是胍丁胺的内源性多胺和代谢产物，没有胍丁胺的胍基部分，未能显示出这种效果，表明这种神经保护作用与结构有关。免疫细胞化学染色和TUNEL测定证实了LDH测量中的结果。也就是说，胍丁胺和MK801显著减轻了NMDA诱导的神经元死亡，并显著减少了培养的海马神经元暴露于NMDA后诱导的TUNEL阳性细胞数量。综上所述，这些结果表明胍丁胺可以通过可能阻断NMDA受体通道或潜在的抗凋亡特性来保护培养的海马神经元免受NMDA或谷氨酸诱导的兴奋性毒性。
