Wee Karen S-L, Zhang Yibin, Khanna Sanjay, Low Chian-Ming
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Republic of Singapore.
J Comp Neurol. 2008 Jul 1;509(1):118-35. doi: 10.1002/cne.21747.
N-methyl-D-aspartate (NMDA) receptors have been implicated in many neurological disorders. Although NMDA receptors are best known for their high calcium permeability, the recently discovered NR3 subunits, NR3A and NR3B, have been shown to reduce the calcium permeability of the NMDA receptor. Thus, NR3 subunits may be important players in modulating synaptic plasticity in neurons. Although NR3B expression in the rodent and human brain has been studied, little is known about its distribution in different cell types. Here we used immunolabeling with a specific NR3B antibody together with antibodies against established neurochemical markers to determine the cellular and subcellular localization of NR3B. The nucleus was concurrently stained with NR3B immunolabeling to show that NR3B is widely expressed by many cells in each brain region. Our findings indicate that NR3B is widely expressed in the structures examined in the rat forebrain (hippocampus, cerebral cortex, caudoputamen, and nucleus accumbens), cerebellum, and lumbar sections of the spinal cord. Within these regions NR3B was found to be expressed in all the substructures of the hippocampus (CA1, CA3, dentate gyrus), the various layers of the cerebral cortex, projection neurons and interneurons of the striatum, different cell types of the cerebellum, and motor neurons of the spinal cord. Furthermore, when stained with NR1-the obligatory subunit responsible for forming functional NMDA receptors-the distribution of NR3B appears to be as ubiquitous as NR1. Taken together, our data suggest that there may be a population of NR3B-containing NMDA receptors conferring new functional roles in the mammalian central nervous system.
N-甲基-D-天冬氨酸(NMDA)受体与许多神经系统疾病有关。尽管NMDA受体因其高钙通透性而最为人所知,但最近发现的NR3亚基,即NR3A和NR3B,已被证明可降低NMDA受体的钙通透性。因此,NR3亚基可能是调节神经元突触可塑性的重要因素。虽然已经对啮齿动物和人类大脑中NR3B的表达进行了研究,但对其在不同细胞类型中的分布却知之甚少。在这里,我们使用针对特定NR3B抗体的免疫标记以及针对已确立的神经化学标志物的抗体,来确定NR3B在细胞和亚细胞水平的定位。同时用NR3B免疫标记对细胞核进行染色,以显示NR3B在每个脑区的许多细胞中广泛表达。我们的研究结果表明,NR3B在大鼠前脑(海马体、大脑皮层、尾状核和伏隔核)、小脑和脊髓腰段的检查结构中广泛表达。在这些区域内,发现NR3B在海马体的所有亚结构(CA1、CA3、齿状回)、大脑皮层的各层、纹状体的投射神经元和中间神经元、小脑的不同细胞类型以及脊髓的运动神经元中均有表达。此外,当用负责形成功能性NMDA受体的必需亚基NR1染色时,NR3B的分布似乎与NR1一样普遍。综上所述,我们的数据表明,可能存在一群含有NR3B的NMDA受体,它们在哺乳动物中枢神经系统中赋予了新的功能作用。