Oh S, Kim Y H, Hann H J, Lee H L, Choi H S, Kim H S, Ho I K
Department of Neuroscience, Medical Research Center, College of Medicine, Ewha Womans University, Seoul, Korea.
Neurochem Res. 2001 May;26(5):559-65. doi: 10.1023/a:1010977315838.
The effects of continuous infusion of NMDA receptor antagonist MK-801 on the modulation of NMDA receptor subunits NR1, NR2A, NR2B, and NR2C were investigated by using in situ hybridization study. Differential assembly of NMDA receptor subunits determines their functional characteristics. Continuous intracerebroventricular (i.c.v.) infusion with MK-801 (1 pmol/10 microl/h) for 7 days resulted in significant modulations in the NR1, NR2A, and NR2B mRNA levels without producing stereotypic motor syndromes. The levels of NR1 mRNA were significantly increased (9-20%) in the cerebral cortex, striatum, septum, and CA1 of hippocampus in MK-801-infused rats. The levels of NR2A mRNA were significantly decreased (11-16%) in the CA3 and dentate gyrus of hippocampus in MK-801-infused rats. In contrast to NR2A, NR2B subunit mRNA levels were increased (10-14%) in the cerebral cortex, caudate putamen, and thalamus. However, no changes of NR2C subunits in cerebellar granule layer were observed. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased (12-25%) significantly in almost all brain regions except in the thalamus and cerebellum after 7 days infusion with MK-801. These results suggest that region-specific changes of NMDA receptor subunit mRNA and [3H]MK-801 binding are involved in the MK-801-infused adult rats.
通过原位杂交研究，调查了持续输注N-甲基-D-天冬氨酸（NMDA）受体拮抗剂MK-801对NMDA受体亚基NR1、NR2A、NR2B和NR2C的调节作用。NMDA受体亚基的差异组装决定了它们的功能特性。连续7天脑室内（i.c.v.）输注MK-801（1皮摩尔/10微升/小时）导致NR1、NR2A和NR2B mRNA水平发生显著调节，且未产生刻板运动综合征。在输注MK-801的大鼠中，大脑皮质、纹状体、隔区和海马CA1区的NR1 mRNA水平显著升高（9 - 20%）。在输注MK-801的大鼠中，海马CA3区和齿状回的NR2A mRNA水平显著降低（11 - 16%）。与NR2A相反，大脑皮质、尾状壳核和丘脑的NR2B亚基mRNA水平升高（10 - 14%）。然而，在小脑颗粒层未观察到NR2C亚基的变化。使用定量配体放射自显影术，在输注MK-801 7天后，除丘脑和小脑外，几乎所有脑区的NMDA受体配体[3H]MK-801结合均显著增加（12 - 25%）。这些结果表明，在输注MK-801的成年大鼠中，NMDA受体亚基mRNA和[3H]MK-801结合的区域特异性变化与之相关。
