{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T22:32:39Z","timestamp":1778365959564,"version":"3.51.4"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81902292"],"award-info":[{"award-number":["81902292"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009991","name":"Jilin Provincial Department of Finance","doi-asserted-by":"publisher","award":["2019SCZ010"],"award-info":[{"award-number":["2019SCZ010"]}],"id":[{"id":"10.13039\/501100009991","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Brain tissue is extremely sensitive to hypoxia\/reoxygenation (H\/R) injury, which can easily cause irreversible damage to neurons. H\/R injury can induce neuronal apoptosis through glutamate-mediated excitotoxicity. N-methyl-d-aspartate receptor (NMDAR) is one of the main receptors of excitatory glutamate, and blocking NMDAR protects brain tissue from ischemic and hypoxic injury. However, NMDAR hypofunction can also cause psychotic symptoms or cognitive impairment. There is still a lack of systematic research on the changes in the proteome and transcriptome in neuronal cells under conditions of NMDAR hypofunction and H\/R injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We compared the changes in the proteome, transcriptome and lncRNA expression levels in neurons after NMDAR knockdown and H\/R by isobaric tags for relative and absolute quantitation (iTRAQ) and RNA sequencing (RNA-Seq).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that the proteins Rps9, Rpl18 and Rpl15 and the lncRNAs XLOC_161072 and XLOC_065271 were significantly downregulated after NMDAR knockdown but upregulated after H\/R; in contrast, the mRNAs Bank1 and Pcp4l1 and the lncRNAs XLOC_159404 and XLOC_031922 were significantly upregulated after NMDAR knockdown but downregulated after H\/R.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In this study, we demonstrated the characterization of protein, mRNA, and lncRNA expression profiles in neurons following NMDAR knockdown and H\/R injury. These molecules are involved in multiple biological functions and signaling pathways, and their roles in neurons lacking NMDAR and subjected to H\/R injury deserve further study. Additionally, we found that lncRNAs respond fastest to hypoxic stimulation and that Gapdh is not suitable as a reference protein for NMDAR-reduced neuron-related experiments.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnmol.2022.1004375","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T05:45:57Z","timestamp":1671083157000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of N-methyl-D-aspartate receptor knockdown and hypoxia\/reoxygenation injury on the neuronal proteome and transcriptome"],"prefix":"10.3389","volume":"15","author":[{"given":"Jinting","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaili","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Sui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiwei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.aca.2018.03.015","article-title":"An amperometric glutamate biosensor for monitoring glutamate release from brain nerve terminals and in blood plasma","volume":"1022","author":"Borisova","year":"2018","journal-title":"Anal. Chim. Acta"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1111\/j.1365-313X.2008.03642.x","article-title":"Selective mRNA translation coordinates energetic and metabolic adjustments to cellular oxygen deprivation and reoxygenation in Arabidopsis thaliana","volume":"56","author":"Branco-Price","year":"2008","journal-title":"Plant J."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1093\/brain\/118.4.1027","article-title":"On the mechanisms underlying hypoxia-induced membrane depolarization in striatal neurons","volume":"118","author":"Calabresi","year":"1995","journal-title":"Brain"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1111\/j.1528-1167.2006.00420.x","article-title":"Alterations in long-term seizure susceptibility and the complex of PSD-95 with NMDA receptor from animals previously exposed to perinatal hypoxia","volume":"47","author":"Chen","year":"2006","journal-title":"Epilepsia"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/s41568-021-00380-y","article-title":"The plasticity of mRNA translation during cancer progression and therapy resistance","volume":"21","author":"Fabbri","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.pneurobio.2006.11.003","article-title":"N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington's disease","volume":"81","author":"Fan","year":"2007","journal-title":"Prog. Neurobiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"5855","DOI":"10.1073\/pnas.1012676108","article-title":"NMDA receptor subunit composition controls synaptogenesis and synapse stabilization","volume":"108","author":"Gambrill","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1113\/JP280875","article-title":"Positive allosteric modulation of NMDA receptors: mechanisms, physiological impact and therapeutic potential","volume":"600","author":"Geoffroy","year":"2022","journal-title":"J. Physiol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.3390\/cells10051184","article-title":"The role of BANK1 in B cell signaling and disease","volume":"10","author":"G\u00f3mez Hern\u00e1ndez","year":"2021","journal-title":"Cells"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"153415","DOI":"10.1016\/j.phymed.2020.153415","article-title":"The potential LXR\u03b2 agonist stigmasterol protects against hypoxia\/reoxygenation injury by modulating mitophagy in primary hippocampal neurons","volume":"81","author":"Haque","year":"2021","journal-title":"Phytomedicine"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1089\/ham.2020.0127","article-title":"NMDA receptor-mediated Excitotoxicity is involved in neuronal apoptosis and cognitive impairment induced by chronic hypobaric hypoxia exposure at high altitude","volume":"22","author":"Ji","year":"2021","journal-title":"High Alt. Med. Biol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"eabc0708","DOI":"10.1126\/sciadv.abc0708","article-title":"Human endogenous retroviral protein triggers deficit in glutamate synapse maturation and behaviors associated with psychosis","volume":"6","author":"Johansson","year":"2020","journal-title":"Sci. Adv."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1111\/j.1750-3639.2005.tb00526.x","article-title":"Excitotoxicity in perinatal brain injury","volume":"15","author":"Johnston","year":"2005","journal-title":"Brain Pathol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1111\/j.1476-5381.2011.01386.x","article-title":"Animal models of schizophrenia","volume":"164","author":"Jones","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/S0006-3223(96)00047-9","article-title":"Psychotogenicity and N-methyl-D-aspartate receptor antagonism: implications for neuroprotective pharmacotherapy","volume":"41","author":"Kornhuber","year":"1997","journal-title":"Biol. Psychiatry"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1056\/NEJM199403033300907","article-title":"Excitatory amino acids as a final common pathway for neurologic disorders","volume":"330","author":"Lipton","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.brainres.2011.03.011","article-title":"The neuroprotective effects of NMDAR antagonist, ifenprodil and ASIC1a inhibitor, flurbiprofen on post-ischemic cerebral injury","volume":"1389","author":"Mishra","year":"2011","journal-title":"Brain Res."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/npp.2011.181","article-title":"From revolution to evolution: the glutamate hypothesis of schizophrenia and its implication for treatment","volume":"37","author":"Moghaddam","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1111\/j.1471-4159.2012.07745.x","article-title":"Pcp 4l1 contains an auto-inhibitory element that prevents its IQ motif from binding to calmodulin","volume":"121","author":"Morgan","year":"2012","journal-title":"J. Neurochem."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"107426","DOI":"10.1016\/j.pharmthera.2019.107426","article-title":"The origin of NMDA receptor hypofunction in schizophrenia","volume":"205","author":"Nakazawa","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"11274","DOI":"10.1073\/pnas.1102429108","article-title":"Endogenous GABA(a) and GABA(B) receptor-mediated electrical suppression is critical to neuronal anoxia tolerance","volume":"108","author":"Pamenter","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.neuron.2014.03.030","article-title":"Extrasynaptic NMDA receptor involvement in central nervous system disorders","volume":"82","author":"Parsons","year":"2014","journal-title":"Neuron"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"417","DOI":"10.3389\/fphys.2019.00417","article-title":"Glutamate transport and preterm brain injury","volume":"10","author":"Pregnolato","year":"2019","journal-title":"Front. Physiol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"103057","DOI":"10.1016\/j.autrev.2022.103057","article-title":"Contemporary advances in anti-NMDAR antibody (Ab)-mediated encephalitis","volume":"21","author":"Seery","year":"2022","journal-title":"Autoimmun. Rev."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"10336","DOI":"10.3390\/ijms231810336","article-title":"Targeting NMDA receptors at the neurovascular unit: past and future treatments for central nervous system diseases","volume":"23","author":"Seillier","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1148\/radiol.2018172083","article-title":"Changes in brain metabolite concentrations after neonatal hypoxic-ischemic encephalopathy","volume":"288","author":"Shibasaki","year":"2018","journal-title":"Radiology"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1111\/ene.14596","article-title":"Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is associated with IRF7, BANK1 and TBX21 polymorphisms in two populations","volume":"28","author":"Shu","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.3233\/JAD-160763","article-title":"Role of glutamate and NMDA receptors in Alzheimer's disease","volume":"57","author":"Wang","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"585584","DOI":"10.3389\/fnins.2020.585584","article-title":"Molecular mechanisms of glutamate toxicity in Parkinson's disease","volume":"14","author":"Wang","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1186\/s13046-018-0974-1","article-title":"Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancer","volume":"37","author":"Xu","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref31","first-page":"1213","article-title":"BQ-869, a novel NMDA receptor antagonist, protects against excitotoxicity and attenuates cerebral ischemic injury in stroke","volume":"8","author":"Yu","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."}],"container-title":["Frontiers in Molecular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2022.1004375\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T05:46:07Z","timestamp":1671083167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2022.1004375\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,15]]},"references-count":31,"alternative-id":["10.3389\/fnmol.2022.1004375"],"URL":"https:\/\/doi.org\/10.3389\/fnmol.2022.1004375","relation":{},"ISSN":["1662-5099"],"issn-type":[{"value":"1662-5099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,15]]},"article-number":"1004375"}}