title: Expression of NMDA receptor and its effect on cell proliferation in the subventricular zone of neonatal rat brain.
abstract: We investigated the involvement of N-methyl D-aspartate receptor (NMDAR) in neurogenesis of rat's subventricular zone (SVZ). For this purpose, we determined expression of the NMDAR subunits NR1, NR2A, and NR2B in SVZ of the neonatal Sprague-Dawley rats using immunohistochemical techniques. All three NMDAR subunits were expressed during postnatal day (PND)-1 to PND-28 whereas each subunit showed a distinct expression pattern. We also examined the functional effect of this receptor on cell proliferation in this region and, in this regard, the animals received either intraperitoneal injection of NMDAR agonist NMDA (2 mg/kg/day) or selective non-competitive NMDAR antagonist MK-801 (10 mg/kg) or NR2B antagonist Ro25-6981 (40 mg/kg), respectively, at PND-3. A significant developmental increase of the total cell density was observed at PND-7 (P < 0.05) while proliferating cell nuclear antigen-positive cell density was significantly increased at PND-14 (P < 0.05) and at PND-28 (P < 0.05) in the SVZ after NMDA (2 mg/kg/day) injection. Our data show that the NMDAR activation promoted the cell proliferation in SVZ during the neonatal period. We, therefore, inferred that NMDAR is expressed in SVZ of the neonatal rat brain and can promote neurogenesis, as through cell proliferation process in that region, and can thus be used as a potential therapeutic target in neurodegenerative diseases.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Fan
authors.forename: Junying
authors.initials: J
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Li
authors.forename: Teijun
authors.initials: T
authors.lastname: Xu
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Yin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D034961:Antigens, Nuclear / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000737:chemistry / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D016202:N-Methylaspartate / Q000819:agonists / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D055495:Neurogenesis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D034961:Antigens, Nuclear; D018691:Excitatory Amino Acid Antagonists; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D018809:Proliferating Cell Nuclear Antigen; D021122:Protein Subunits; C546339:Rbfox3 protein, rat; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate