【作者】 田映红；

【导师】 高天明；

【作者基本信息】 第一军医大学 ， 神经生物学， 2006， 博士

【摘要】 NMDAR（N-methyl-D-aspartate receptors，NMDAR）是中枢神经系统中离子型谷氨酸受体的一种类型，对Ca²⁺有高通透性。生理状态的NMDAR参与细胞存活，神经元迁移，突触形成，突触传递和突触可塑（如学习和记忆）。急性神经损伤如脑损伤、脑缺血、低血糖、缺氧、癫痫以及慢性神经退化疾病中神经元损害的病理过程也与NMDAR密切相关。 NMDAR包括NR1，NR2和NR3三种亚单位。NR1有3个剪接位点，能形成8种异构体。NR2分为4种亚型，分别是NR2A，NR2B，NR2C，NR2D。NR3有两种亚型，即NR3A和NR3B。有功能的NMDAR主要由2个NR1和2个NR2亚单位组成，其中NR2亚单位决定受体的许多特性。 NMDAR各亚单位的mRNA在脑内的分布不同，并且还有发育变化。在胚胎脑内，只表达NR2B和NR2D mRNA。NR2A和NR2C mRNA在出生时才开始表达。生后两周，NR2A mRNA在整个脑内广泛表达，NR2C mRNA在小脑表达。NR2B mRNA的表达局限在前脑，而NR2D mRNA的表达局限在丘脑，脑干和嗅球。NR1mRNA在整个发育期都广泛在全脑表达。在突触内外，NMDAR各亚单位的分布也存在发育变化。在发育早期突触内外的NMDAR主要为NR1／NR2B，其全细胞电流对NR2B的特异拮抗剂ifenprodil很敏感。在生后第二周突触内开始出现NR2A，形成NR1／NR2A／NR2B三聚体，并且NR2A比NR2B的表达要高很多，突触外仍主要表现为NR2B。NR2C仅在小脑颗粒细胞的突触内大量存在，NR2D一般只存在于突触外。海马和皮层神经元的NR2亚单位主要是NR2A和NR2B。 以前的研究认为NMDAR参与兴奋毒诱导神经元损伤的可能机制是NMDAR更多还原

【Abstract】 N-methyl-D-aspartate receptors （NMDARs） is one of ionotropic glutamatergic receptors. Their unique features include voltage-sensitive block by extracellular Mg²⁺, a high permeability to Ca²⁺ Physiological NMDARs are critical players in cell survival, neuronal migration, synaptogenesis, synaptic transmission and synaptic plasticity such as learning and memory, while their excessive activation is thought to be responsible for neuronal cell damage during acute neurological conditions such as brain trauma, cerebral ischaemia, hypoglycaemia, hypoxia and epileptic seizures; as well as during chronic neurodegenerative diseases.A variety of NMDAR subunits have been identified: the ubiquitously expressed NRl subunit; a family of four distinct NR2 subunits（A, B, C and D）; and two NR3 subunits. NRl occurs as eight distinct isoforms owing to the presence of three independent sites of alternative splicing. NR3 has two isoforms（NR3A and NR3B）. Functional NMDARs are heteromeric assemblies composed of 2 NRl subunits and at least one type of NR2. Many of the important functional attributes of the native receptors are determined by the expression of the various NR2 subunits.The distribution of NMDAR subunits mRNAs in brain is different and changes with development. NR2B and NR2D mRNAs occur prenatally, whereas NR2A and NR2C mRNAs are first detected near birth. During the second postnatal week, NR2A mRNAs are ubiquitously更多还原