Riva M A, Tascedda F, Molteni R, Racagni G
DIBIT, San Raffaele Hospital, Milan, Italy.
Brain Res Mol Brain Res. 1994 Sep;25(3-4):209-16. doi: 10.1016/0169-328x(94)90155-4.
Different NMDA receptor subunits have been recently cloned. The present paper describes the developmental profile of expression of the NR-1 subunit and three NR-2 subunits (A, B, C) in the rat central nervous system. A sensitive RNase protection assay was employed to determine simultaneously the mRNA levels of these receptor subunits. We found low levels of NR-1 mRNA (comprising all different splicing isoforms) in newborn rats with a progressive increase of its expression in the following 2-3 weeks. NR-2 subunits can be regarded as 'modulatory' since their expression can produce differences in the properties of NMDA receptors. More than one NR-2 subunits can be expressed in the same brain region. NR-2A and NR-2C are concomitantly expressed in the cerebellum and during development their mRNAs increase with a similar profile from low levels in P-8 rats to maximal expression in P-21 animals. NR-2A and NR-2B are concomitantly expressed in several brain regions with a different ontogenetic profile. In the hippocampus NR-2B mRNA increases rapidly during the first week of life as compared to the NR-2A subunits which at this time is expressed to low levels indicating that NR-2B will probably be dominant in determining the NMDA properties during the first period of life. Our data can provide a molecular correlate with properties of NMDA receptors such as voltage dependent Mg2+ block and deactivation kinetics which undergo significant changes during development and have been shown to depend upon the NR-2 subunit co-expressed with the common NR-1 subunit in various brain regions.
不同的N-甲基-D-天冬氨酸（NMDA）受体亚基最近已被克隆。本文描述了NR-1亚基和三个NR-2亚基（A、B、C）在大鼠中枢神经系统中的表达发育情况。采用灵敏的核糖核酸酶保护试验同时测定这些受体亚基的mRNA水平。我们发现新生大鼠中NR-1 mRNA水平较低（包括所有不同的剪接异构体），在随后的2至3周内其表达逐渐增加。NR-2亚基可被视为“调节性”亚基，因为它们的表达可使NMDA受体的特性产生差异。不止一种NR-2亚基可在同一脑区表达。NR-2A和NR-2C在小脑中同时表达，在发育过程中它们的mRNA从出生后8天（P-8）大鼠的低水平开始以相似的模式增加，至出生后21天（P-21）动物时达到最大表达。NR-2A和NR-2B在几个脑区同时表达，但个体发育模式不同。在海马体中，与此时低水平表达的NR-2A亚基相比，NR-2B mRNA在出生后的第一周迅速增加，这表明在生命的第一阶段，NR-2B可能在决定NMDA特性方面占主导地位。我们的数据可以为NMDA受体的特性提供分子关联，例如电压依赖性Mg2+阻断和失活动力学，这些特性在发育过程中会发生显著变化，并且已被证明取决于在不同脑区与共同的NR-1亚基共表达的NR-2亚基。
