Different Roles Of Synaptic And Extrasynaptic NMDA Receptors In Oxygen-Glucose Deprivation Induced Neuronal Damage

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...