title: The GluN3A subunit exerts a neuroprotective effect in brain ischemia and the hypoxia process.
abstract: NMDARs (N-methyl-D-aspartate receptors) mediate the predominantly excitatory neurotransmission in the CNS (central nervous system). Excessive release of glutamate and overactivation of NMDARs during brain ischemia and the hypoxia process are causally linked to excitotoxicity and neuronal damage. GluN3 subunits, the third member of the NMDAR family with two isoforms, GluN3A and GluN3B, have been confirmed to display an inhibitory effect on NMDAR activity. However, the effect of GluN3 subunits in brain ischemia and hypoxia is not clearly understood. In the present study, the influence of ischemia and hypoxia on GluN3 subunit expression was observed by using the 2VO (two-vessel occlusion) rat brain ischemia model and cell OGD (oxygen and glucose deprivation) hypoxia model. It was found that GluN3A protein expression in rat hippocampus and the prefrontal cortex was increased quickly after brain ischemia and remained at a high level for at least 24 h. However, the expression of the GluN3B subunit was not remarkably changed in both the animal and cell models. After OGD exposure, rat hippocampal neurons with GluN3A subunit overexpression displayed more viability than the wild-type neurons. NG108-15 cells overexpressing GluN3A presented pronounced resistance to glutamate insult. Blocking the increase of intracellular Ca2+ concentration may underlie the neuroprotective mechanism of up-regulated GluN3A subunit. Suppressing the generation of hydroxyl radicals and NO (nitric oxide) is probably also involved in the neuroprotection.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Haitao
authors.initials: H
authors.lastname: Yan
authors.forename: Shuzhuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wei
authors.forename: Jianquan
authors.initials: J
authors.lastname: Zheng
authors.forename: Jin
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics; D019610:Cytoprotection / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate