反义寡聚核苷酸对神经元兴奋性毒性的拮抗作用

Effects of antisense oligonucleotides for N-methyl-D-aspartate receptor 1 on protection of cerebrocortical neurons from excitotoxicity

为探讨Ｎ－甲基－Ｄ－天门冬氨酸受体的Ⅰ型亚基在兴奋性神经毒性损伤中的作用在大鼠大脑皮层神经元原代增减中，钭细胞分为反义，正义ＮＲ１寡聚核苷酸，脂质体及正常对照组，分别给药，通过细胞计数，扫描电镜，放射性受体分析技术观察神经元形态及功能。

Excessive activation of N-methyl-D-aspartate (NMDA) receptors has been implicated in excitotoxicity of acute as well as chronic neuropathological processes. In this study, we administered an antisense oligonucleotides for N-methyl-D-aspartate receptor 1 (NR1) or the correspondent sense oligonucleotides to cultured cerebrocortical neurons to investigate the role of antisense oligonucleotides for NR1 in excitotoxicity of neuropathological processes. The results showed that pretreatment with NR1 antisense oligonueleotides (2μmol/L) preseved more than 52 % of glutamate-sensitive neurons including reduced occurrence of fragmentation of dendrite and axon and cell body damage, and caused reduction of[~3H]MK-801 binding to cultured cerehrcortical neurons by 50%. These results suggested that NR1 antisense could suppress excitotoxicity, which was associated with down-regulation of NMDA receptor.