title: A neuroprotective role of the NMDA receptor subunit GluN3A (NR3A) in ischemic stroke of the adult mouse.
abstract: GluN3A or NR3A is a developmentally regulated N-methyl-d-aspartate receptor (NMDAR) subunit, showing a unique inhibitory role that decreases NMDAR current and the receptor-mediated Ca(2+) influx. In the neonatal brain, GluN3A is shown to associate with synaptic maturation and spine formation and plays a neuroprotective role. Its functional role in the adult brain, however, is largely unknown. We tested the hypothesis that, disrespecting the relatively lower expression level of GluN3A in the adult brain, this inhibitory NMDAR subunit shows a protective action against ischemia-induced brain injury. In littermate wild-type (WT) and GluN3A knockout (KO) mice, focal cerebral ischemia was induced by permanent occlusion of right distal branches of the middle cerebral artery (MCA) plus 10-min ligation of both common carotid arteries (CCAs). Twenty-four hours after focal cerebral ischemia, the infarction volume assessed using 2,3,5-triphenyltetrazolium chloride (TTC) staining was significantly larger in GluN3A KO mice compared with WT mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining demonstrated enhanced cell death in GluN3A KO mice. Moreover, the deletion of GluN3A hindered sensorimotor functional recovery after stroke. It is suggested that, although the expression level is relatively lower in the adult brain, GluN3A is still a noteworthy regulator in ischemia-induced excitotoxicity and brain injury.
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia; and.
authors: Jin Hwan
authors: http://orcid.org/0000-0001-6975-2479
authors: JH
authors: Lee
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia; and Center for Visual and Neurocognitive Rehabilitation, Atlanta Veterans Affairs Medical Center, Decatur, Georgia.
authors: Zheng Z
authors: ZZ
authors: Wei
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia; and Center for Visual and Neurocognitive Rehabilitation, Atlanta Veterans Affairs Medical Center, Decatur, Georgia.
authors: Dongdong
authors: D
authors: Chen
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia; and Center for Visual and Neurocognitive Rehabilitation, Atlanta Veterans Affairs Medical Center, Decatur, Georgia.
authors: Xiaohuan
authors: X
authors: Gu
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia; and Center for Visual and Neurocognitive Rehabilitation, Atlanta Veterans Affairs Medical Center, Decatur, Georgia.
authors: Ling
authors: L
authors: Wei
authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia; and Center for Visual and Neurocognitive Rehabilitation, Atlanta Veterans Affairs Medical Center, Decatur, Georgia spyu@emory.edu.
authors: Shan Ping
authors: SP
authors: Yu
mesh_terms: D000367:Age Factors; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control*; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D021122:Protein Subunits / Q000172:deficiency*; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency*; D020521:Stroke / Q000378:metabolism* / Q000517:prevention & control*
chemical_list: C464437:NR3A NMDA receptor; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate
keywords: GluN3A; NMDA receptors; adult brain; functional recovery; stroke
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