Cai Z, Rhodes P G
Department of Pediatrics/Newborn Medicine, University of Mississippi Medical Center, Jackson 39216, USA.
Neurochem Res. 2001 May;26(5):487-95. doi: 10.1023/a:1010904727225.
Effects of intrauterine hypoxia-ischemia (HI) on expression of the NMDA receptor subunits as well as on [3H]MK-801 binding of the NMDA receptor were studied in 1-day to 30-day old rat brain. Intrauterine HI conditions were achieved on gestation day 17 by clamping the uterine vasculature for 30 min followed by removal of the clamps to permit reperfusion. As determined by reverse-transcriptase polymerase chain reaction, prenatal HI significantly reduced mRNA expression of the NRI subunit of the NMDA receptor in the hippocampus of 4, 8, and 30-day old rat brains. NR2A and NR2B subunit mRNAs were expressed in the hippocampus and the cortex of both the control and the prenatal HI rat brains. Intrauterine HI did not significantly affect expression of either the NR2A or NR2B subunit mRNA. Consistent with the RT-PCR data, protein expression of the NRI subunit in the hippocampus, but not the cortex, of 21-day old prenatal HI rat brains was significantly decreased as compared to the control rat brain. Intrauterine HI also significantly reduced binding affinity, but not the number of binding sites, of the NMDA receptor to [3H]MK-801, a noncompetitive antagonist of the NMDA receptor, in the hippocampus of 21-day old rat brain. The overall results suggest that prenatal HI-induced reduction of NRI expression and the altered binding ability of the NMDA receptor in the young rat brain may contribute to other long-lasting effects of intrauterine HI that we reported previously.
在1日龄至30日龄大鼠脑中，研究了宫内缺氧缺血（HI）对NMDA受体亚基表达以及NMDA受体与[3H]MK-801结合的影响。在妊娠第17天，通过钳夹子宫血管30分钟，随后移除夹子以允许再灌注，从而实现宫内HI条件。通过逆转录聚合酶链反应测定，产前HI显著降低了4日龄、8日龄和30日龄大鼠脑海马中NMDA受体NRI亚基的mRNA表达。NR2A和NR2B亚基mRNA在对照和产前HI大鼠脑的海马和皮质中均有表达。宫内HI对NR2A或NR2B亚基mRNA的表达均无显著影响。与逆转录聚合酶链反应数据一致，与对照大鼠脑相比，21日龄产前HI大鼠脑海马而非皮质中NRI亚基的蛋白表达显著降低。宫内HI还显著降低了21日龄大鼠脑海马中NMDA受体与[3H]MK-801（一种NMDA受体非竞争性拮抗剂）的结合亲和力，但不影响结合位点的数量。总体结果表明，产前HI诱导的幼鼠脑内NRI表达降低以及NMDA受体结合能力改变，可能导致我们之前报道的宫内HI的其他长期影响。
