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Cited by 9Neuroscience and Neuropharmacology ResearchPain Mechanisms and TreatmentsIon channel regulation and function

Pluripotential GluN1 (NMDA NR1): Functional Significance in Cellular Nuclei in Pain/Nociception

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McNearney, Terry A., Westlund, Karin N.·2023·International Journal of Molecular Sciences
DOI 10.3390/ijms241713196PMC PMC10488196
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Abstract

The N-methyl-D-aspartate (NMDA) glutamate receptors function as plasma membrane ionic channels and take part in very tightly controlled cellular processes activating neurogenic and inflammatory pathways. In particular, the NR1 subunit (new terminology: GluN1) is required for many neuronal and non-neuronal cell functions, including plasticity, survival, and differentiation. Physiologic levels of glutamate agonists and NMDA receptor activation are required for normal neuronal functions such as neuronal development, learning, and memory. When glutamate receptor agonists are present in excess, binding to NMDA receptors produces neuronal/CNS/PNS long-term potentiation, conditions of acute pain, ongoing severe intractable pain, and potential excitotoxicity and pathology. The GluNR1 subunit (116 kD) is necessary as the anchor component directing ion channel heterodimer formation, cellular trafficking, and the nuclear localization that directs functionally specific heterodimer formation, cellular trafficking, and nuclear functions. Emerging studies report the relevance of GluN1 subunit composition and specifically that nuclear GluN1 has major physiologic potential in tissue and/or subnuclear functioning assignments. The shift of the GluN1 subunit from a surface cell membrane to nuclear localization assigns the GluN1 promoter immediate early gene behavior with access to nuclear and potentially nucleolar functions. The present narrative review addresses the nuclear translocation of GluN1, focusing particularly on examples of the role of GluN1 in nociceptive processes.

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  • Previous studies have shown that non-neuronal cells can regulate central sensitization by modulating synaptic plasticity.

    “Previous studies have shown that non-neuronal cells can regulate central sensitization by modulating synaptic plasticity (12, 13).”

    From Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization (2026) · cites this paper as [13]

    The Introduction (page unavailable) reports activated non-neuronal cells in contexts relevant to pain and describes NMDA receptors as important to synaptic plasticity. Section 3 (page unavailable) reports that blocking NMDA receptors reversed sensitization of dorsal horn neurons. The review does not establish the claimed link—that non-neuronal cells regulate central sensitization by modulating synaptic plasticity. (LLM, conf=0.72)

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  1. [1]Harding S.D. Armstrong J.F. Faccenda E. Southan C. Alexander S.P.H. Davenport A.P. Pawson A.J. Spedding M. Davies J.A. Iuphar N. The IUPHAR/BPS guide to PHARMACOLOGY in 2022: Curating pharmacology for COVID-19, malaria and antibacterials Nucleic Acids Res. 2021 50 D1282 D1294 10.1093/nar/gkab1010 PMC8689838 34718737 · DOI · Paper page
  2. [2]Marini A.M. Rabin S.J. Lipsky R.H. Mocchetti I. Activity-dependent Release of Brain-derived Neurotrophic Factor Underlies the Neuroprotective Effect of N-Methyl-d-aspartate J. Biol. Chem. 1998 273 29394 29399 10.1074/jbc.273.45.29394 9792641 · DOI
  3. [3]Hansen K.B. Wollmuth L.P. Bowie D. Furukawa H. Menniti F.S. Sobolevsky A.I. Swanson G.T. Swanger S.A. Greger I.H. Nakagawa T. Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels Pharmacol. Rev. 2021 73 1469 1658 10.1124/pharmrev.120.000131 PMC8626789 34753794 · DOI · Paper page
  4. [4]Chandrasekar R. Alcohol and NMDA receptor: Current research and future direction Front. Mol. Neurosci. 2013 6 14 10.3389/fnmol.2013.00014 23754976 PMC3664776 · DOI
  5. [5]Bai G. Hoffman P.W. Chapter 5 Biology of the NMDA Receptor Van Dongen A.M. CRC Press Taylor & Francis Boca Raton, FL, USA 2009
  6. [6]Willis W.D. Jr. The role of TRPV1 receptors in pain evoked by noxious thermal and chemical stimuli Exp. Brain Res. 2009 196 5 11 10.1007/s00221-009-1760-2 19294370 · DOI
  7. [7]Kristensen J.D. Svensson B. Gordh T. The NMDA-receptor antagonist CPP abolishes neurogenic ‘wind-up pain’ after intrathecal administration in humans Pain 1992 51 249 253 10.1016/0304-3959(92)90266-E 1484720 · DOI
  8. [8]Riccardi A. Guarino M. Serra S. Spampinato M.D. Vanni S. Shiffer D. Voza A. Fabbri A. De Iaco F. on behalf of the Study and Research Center of the Italian Society of Emergency Medicine Narrative Review: Low-Dose Ketamine for Pain Management J. Clin. Med. 2023 12 3256 10.3390/jcm12093256 37176696 PMC10179418 · DOI
  9. [9]South S.M. Kohno T. Kaspar B.K. Hegarty D. Vissel B. Drake C.T. Ohata M. Jenab S. Sailer A.W. Malkmus S. A Conditional Deletion of the NR1 Subunit of the NMDA Receptor in Adult Spinal Cord Dorsal Horn Reduces NMDA Currents and Injury-Induced Pain J. Neurosci. 2003 23 5031 5040 10.1523/JNEUROSCI.23-12-05031.2003 12832526 PMC6741202 · DOI
  10. [10]Hietamies T.M. McInnes L.A. Klise A.J. Worley M.J. Qian J.J. Williams L.M. Heifets B.D. Levine S.P. The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis J. Affect. Disord. 2023 335 484 492 10.1016/j.jad.2023.04.141 37201900 · DOI
  11. [11]Yang J. Hertz E. Zhang X. Leinartaité L. Lundius E.G. Li J. Svenningsson P. Overexpression of α-synuclein simultaneously increases glutamate NMDA receptor phosphorylation and reduces glucocerebrosidase activity Neurosci. Lett. 2016 611 51 58 10.1016/j.neulet.2015.11.023 26610904 · DOI
  12. [12]Zhang Z. Zhang S. Fu P. Zhang Z. Lin K. Ko J.K.-S. Yung K.K.-L. Roles of Glutamate Receptors in Parkinson’s Disease Int. J. Mol. Sci. 2019 20 4391 10.3390/ijms20184391 31500132 PMC6769661 · DOI
  13. [13]Lewerenz J. Maher P. Chronic Glutamate Toxicity in Neurodegenerative Diseases—What Is the Evidence? Front. Neurosci. 2015 9 469 10.3389/fnins.2015.00469 26733784 PMC4679930 · DOI
  14. [14]Lipton S.A. NMDA Receptors, Glial Cells, and Clinical Medicine Neuron 2006 50 9 11 10.1016/j.neuron.2006.03.026 16600850 · DOI
  15. [15]Nagu P. Parashar A. Behl T. Mehta V. Gut Microbiota Composition and Epigenetic Molecular Changes Connected to the Pathogenesis of Alzheimer’s Disease J. Mol. Neurosci. 2021 71 1436 1455 10.1007/s12031-021-01829-3 33829390 · DOI
  16. [16]Rodríguez-Muñoz M. Sánchez-Blázquez P. Garzón J. Fenfluramine diminishes NMDA receptor-mediated seizures via its mixed activity at serotonin 5HT2A and type 1 sigma receptors Oncotarget 2018 9 23373 23389 10.18632/oncotarget.25169 29805740 PMC5955088 · DOI
  17. [17]Levite M. Goldberg H. Autoimmune Epilepsy—Novel Multidisciplinary Analysis, Discoveries and Insights Front. Immunol. 2022 12 762743 10.3389/fimmu.2021.762743 35095841 PMC8790247 · DOI
  18. [18]Holmes K.D. Mattar P. Marsh D.R. Jordan V. Weaver L.C. Dekaban G.A. The C-terminal C1 cassette of the N-methyl-d-aspartate receptor 1 subunit contains a bi-partite nuclear localization sequence J. Neurochem. 2002 81 1152 1165 10.1046/j.1471-4159.2002.00865.x 12068064 · DOI
  19. [19]Zhou L. Duan J. The NMDAR GluN1-1a C-terminus binds to CaM and regulates synaptic function Biochem. Biophys. Res. Commun. 2021 534 323 329 10.1016/j.bbrc.2020.11.085 33248694 · DOI
  20. [20]Ulbrich M.H. Isacoff E.Y. Rules of engagement for NMDA receptor subunits Proc. Natl. Acad. Sci. USA 2008 105 14163 14168 10.1073/pnas.0802075105 18779583 PMC2544595 · DOI
  21. [21]Jeffrey R.A. Ch’Ng T.H. O’Dell T.J. Martin K.C. Activity-Dependent Anchoring of Importin α at the Synapse Involves Regulated Binding to the Cytoplasmic Tail of the NR1-1a Subunit of the NMDA Receptor J. Neurosci. 2009 29 15613 15620 10.1523/JNEUROSCI.3314-09.2009 20016075 PMC2819930 · DOI
  22. [22]Niu M. Yang X. Li Y. Sun Y. Wang L. Ha J. Xie Y. Gao Z. Tian C. Wang L. Progresses in GluN2A-containing NMDA Receptors and their Selective Regulators Cell. Mol. Neurobiol. 2023 43 139 153 10.1007/s10571-021-01185-1 34978648 PMC11415211 · DOI
  23. [23]Zhou L. Duan J. The C-terminus of NMDAR GluN1-1a Subunit Translocates to Nucleus and Regulates Synaptic Function Front. Cell. Neurosci. 2018 12 334 10.3389/fncel.2018.00334 30333730 PMC6176477 · DOI
  24. [24]Garraway S.M. Xu Q. Inturrisi C.E. Design and Evaluation of Small Interfering RNAs That Target Expression of the N-Methyl-d-aspartate Receptor NR1 Subunit Gene in the Spinal Cord Dorsal Horn Experiment 2007 322 982 988 10.1124/jpet.107.123125 17551091 · DOI
  25. [25]Samra Y.A. Kira D. Rajpurohit P. Mohamed R. Owen L.A. Shakoor A. Kim I.K. DeAngelis M.M. Sheibani N. Al-Shabrawey M. Implication of N-Methyl-d-Aspartate Receptor in Homocysteine-Induced Age-Related Macular Degeneration Int. J. Mol. Sci. 2021 22 9356 10.3390/ijms22179356 34502266 PMC8431693 · DOI
  26. [26]Mashkina A.P. Cizkova D. Vanicky I. Boldyrev A.A. NMDA Receptors are Expressed in Lymphocytes Activated Both In Vitro and In Vivo Cell. Mol. Neurobiol. 2010 30 901 907 10.1007/s10571-010-9519-7 20414717 PMC11498795 · DOI
  27. [27]McNearney T.A. Ma Y. Chen Y. Taglialatela G. Yin H. Zhang W.-R. Westlund K.N. A peripheral neuroimmune link: Glutamate agonists upregulate NMDA NR1 receptor mRNA and protein, vimentin, TNF-α, and RANTES in cultured human synoviocytes Am. J. Physiol. Integr. Comp. Physiol. 2010 298 R584 R598 10.1152/ajpregu.00452.2009 PMC2838657 20007519 · DOI
  28. [28]Flood S. Parri R. Williams A. Duance V. Mason D. Modulation of interleukin-6 and matrix metalloproteinase 2 expression in human fibroblast-like synoviocytes by functional ionotropic glutamate receptors Arthritis Rheum. 2007 56 2523 2534 10.1002/art.22829 17665433 · DOI
  29. [29]Baatout S. Chatelain B. Staquet P. Symann M. Chatelain C. Interaction between protein kinase C and actin in megakaryocyte polyploidization Anticancer Res. 1999 19 4193 4198 10628374
  30. [30]Hitchcock I.S. Skerry T.M. Howard M.R. Genever P.G. NMDA receptor–mediated regulation of human megakaryocytopoiesis Blood 2003 102 1254 1259 10.1182/blood-2002-11-3553 12649130 · DOI
  31. [31]Chenu C. Serre C. Raynal C. Burt-Pichat B. Delmas P. Glutamate Receptors Are Expressed by Bone Cells and Are Involved in Bone Resorption Bone 1998 22 295 299 10.1016/S8756-3282(97)00295-0 9556127 · DOI
  32. [32]Ghosh K. Pan H.-L. Epigenetic Mechanisms of Neural Plasticity in Chronic Neuropathic Pain ACS Chem. Neurosci. 2022 13 432 441 10.1021/acschemneuro.1c00841 35107991 PMC13294747 · DOI
  33. [33]Nasca C. Zelli D. Bigio B. Piccinin S. Scaccianoce S. Nisticò R. McEwen B.S. Stress dynamically regulates behavior and glutamatergic gene expression in hippocampus by opening a window of epigenetic plasticity Proc. Natl. Acad. Sci. USA 2015 112 14960 14965 10.1073/pnas.1516016112 26627246 PMC4672825 · DOI
  34. [34]Gascón S. Deogracias R. Sobrado M. Roda J.M. Renart J. Rodríguez-Peña A. Díaz-Guerra M. Transcription of the NR1 Subunit of the N-Methyl-d-aspartate Receptor Is Down-regulated by Excitotoxic Stimulation and Cerebral Ischemia J. Biol. Chem. 2005 280 35018 35027 10.1074/jbc.M504108200 16049015 · DOI
  35. [36]Zidovska A. The rich inner life of the cell nucleus: Dynamic organization, active flows, and emergent rheology Biophys. Rev. 2020 12 1093 1106 10.1007/s12551-020-00761-x 33064286 PMC7575674 · DOI
  36. [37]Hua L. Yan D. Wan C. Hu B. Nucleolus and Nucleolar Stress: From Cell Fate Decision to Disease Development Cells 2022 11 3017 10.3390/cells11193017 36230979 PMC9563748 · DOI
  37. [38]Holmes K.D. Mattar P.A. Marsh D.R. Weaver L.C. Dekaban G.A. The N-Methyl-d-aspartate Receptor Splice Variant NR1–4 C-terminal Domain. Deletion analysis and role in subcellular distribution J. Biol. Chem. 2002 277 1457 1468 10.1074/jbc.M107809200 11700309 · DOI
  38. [39]Thompson K.R. Otis K.O. Chen D.Y. Zhao Y. O’Dell T.J. Martin K.C. Synapse to Nucleus Signaling during Long-Term Synaptic Plasticity: A Role for the Classical Active Nuclear Import Pathway Neuron 2004 44 997 1009 10.1016/j.neuron.2004.11.025 15603742 · DOI
  39. [40]Westlund K.N. Lu Y. Zhang L. Pappas T.C. Zhang W.-R. Taglialatela G. McIlwrath S.L. McNearney T.A. Tyrosine Kinase Inhibitors Reduce NMDA NR1 Subunit Expression, Nuclear Translocation, and Behavioral Pain Measures in Experimental Arthritis Front. Physiol. 2020 11 440 10.3389/fphys.2020.00440 32536874 PMC7267073 · DOI
  40. [41]Lawand N.B. McNearney T. Westlund K.N. Amino acid release into the knee joint: Key role in nociception and inflammation Pain 2000 86 69 74 10.1016/S0304-3959(99)00311-5 10779662 · DOI
  41. [42]Sorkin L. Westlund K. Sluka K. Dougherty P. Willis W. Neural changes in acute arthritis in monkeys. IV. Time-course of amino acid release into the lumbar dorsal horn Brain Res. Rev. 1992 17 39 50 10.1016/0165-0173(92)90005-7 1638274 · DOI
  42. [43]Pol A.N.v.D. Obrietan K. Chen G. Excitatory Actions of GABA after Neuronal Trauma J. Neurosci. 1996 16 4283 4292 10.1523/jneurosci.16-13-04283.1996 8753889 PMC6578987 · DOI
  43. [44]Coull J.A.M. Boudreau D. Bachand K. Prescott S.A. Nault F. Sík A. De Koninck P. De Koninck Y. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain Nature 2003 424 938 942 10.1038/nature01868 12931188 · DOI
  44. [45]Ye Z. Westlund K.N. Ultrastructural localization of glutamate receptor subunits (NMDAR1, AMPA GluR1 and GluR2/3) and spinothalamic tract cells Neuroreport 1996 7 2581 2586 10.1097/00001756-199611040-00035 8981427 · DOI
  45. [46]Satoh T. Nakatsuka D. Watanabe Y. Nagata I. Kikuchi H. Namura S. Neuroprotection by MAPK/ERK kinase inhibition with U0126 against oxidative stress in a mouse neuronal cell line and rat primary cultured cortical neurons Neurosci. Lett. 2000 288 163 166 10.1016/S0304-3940(00)01229-5 10876086 · DOI
  46. [47]Li J. Yan D. Liu X. Wang Y. Zhao X. Zhang Y. Zhang C. U0126 protects hippocampal CA1 neurons against forebrain ischemia-induced apoptosis via the ERK1/2 signaling pathway and NMDA receptors Neurol. Res. 2018 40 318 323 10.1080/01616412.2018.1441693 29473447 · DOI
  47. [48]Sluka K. Jordan H. Willis W. Westlund K. Differential effects of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on spinal release of amino acids after development of acute arthritis in rats Brain Res. 1994 664 77 84 10.1016/0006-8993(94)91956-9 7895049 · DOI
  48. [49]Lucke T. Schaible H.-G. Zhang J. Mense S. Treede R.-D. Hoheisel U. Sun R.-Q. Lawand N.B. Lin Q. Willis W.D. N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists block the hyperexcitability of dorsal horn neurons during development of acute arthritis in rat’s knee joint J. Neurophysiol. 1993 70 1365 1377 10.1152/jn.1993.70.4.1365 7904298 · DOI
  49. [50]Skilling S.R. Smullin D.H. Beitz A.J. Larson A.A. Extracellular Amino Acid Concentrations in the Dorsal Spinal Cord of Freely Moving Rats Following Veratridine and Nociceptive Stimulation J. Neurochem. 1988 51 127 132 10.1111/j.1471-4159.1988.tb04845.x 2898001 · DOI
  50. [51]McNearney T. Speegle D. Lawand N. Lisse J. Westlund K.N. Excitatory amino acid profiles of synovial fluid from patients with arthritis J. Rheumatol. 2000 27 739 745 10743819 PMC7894989
  51. [52]Botto R. Callai N. Cermelli A. Causarano L. Rainero I. Anxiety and depression in Alzheimer’s disease: A systematic review of pathogenetic mechanisms and relation to cognitive decline Neurol. Sci. 2022 43 4107 4124 10.1007/s10072-022-06068-x 35461471 PMC9213384 · DOI
  52. [53]Flood P.M. Qian L. Peterson L.J. Zhang F. Shi J.-S. Gao H.-M. Hong J.-S. Transcriptional Factor NF-κB as a Target for Therapy in Parkinson’s Disease Park. Dis. 2011 2011 1 8 10.4061/2011/216298 21603248 PMC3095232 · DOI
  53. [54]Liu Y.-J. Li Y.-L. Fang Z.-H. Liao H.-L. Zhang Y.-Y. Lin J. Liu F. Shen J.-F. NMDARs mediate peripheral and central sensitization contributing to chronic orofacial pain Front. Cell. Neurosci. 2022 16 999509 10.3389/fncel.2022.999509 36238833 PMC9553029 · DOI
  54. [55]Lipsky R.H. Xu K. Zhu D. Kelly C. Terhakopian A. Novelli A. Marini A.M. Nuclear factor κB is a critical determinant in N-methyl-d-aspartate receptor-mediated neuroprotection J. Neurochem. 2001 78 254 264 10.1046/j.1471-4159.2001.00386.x 11461961 · DOI
  55. [56]Lee I.-O. Yukhananov R. Standaert D.G. Crosby G. NMDA-R1 antisense oligodeoxynucleotides modify formalin-induced nociception and spinal c-Fos expression in rat spinal cord Pharmacol. Biochem. Behav. 2004 79 183 188 10.1016/j.pbb.2004.07.003 15388298 · DOI
  56. [57]Peet N.M. Grabowski P.S. Laketić-Ljubojević I. Skerry T.M. The glutamate receptor antagonist MK801 modulates bone resorption in vitro by a mechanism predominantly involving osteoclast differentiation FASEB J. 1999 13 2179 2185 10.1096/fasebj.13.15.2179 10593865 · DOI
  57. [58]Tan P.-H. Yu S.-W. Lin V.C.-H. Liu C.-C. Chien C.-F.C. RNA interference-mediated gene silence of the NR1 subunit of the NMDA receptor by subcutaneous injection of vector-encoding short hairpin RNA reduces formalin-induced nociception in the rat Pain 2011 152 573 581 10.1016/j.pain.2010.11.026 21239115 · DOI
  58. [59]Sluka K. Westlund K. An experimental arthritis model in rats: The effects of NMDA and non-NMDA antagonists on aspartate and glutamate release in the dorsal horn Neurosci. Lett. 1993 149 99 102 10.1016/0304-3940(93)90357-Q 8097022 · DOI
  59. [60]Salter M.G. Fern R. NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury Nature 2005 438 1167 1171 10.1038/nature04301 16372012 · DOI
  60. [61]Peng J.-M. Xu L.-S. Zhu Q. Gong S. Yu X.-M. Guo S.-Y. Wu G.-C. Tao J. Jiang X.-H. Enhanced NMDA receptor NR1 phosphorylation and neuronal activity in the arcuate nucleus of hypothalamus following peripheral inflammation Acta Pharmacol. Sin. 2011 32 160 166 10.1038/aps.2010.190 21293467 PMC4009944 · DOI
  61. [62]Zhou Q. Price D.D. Caudle R.M. Verne G.N. Spinal NMDA NR1 subunit expression following transient TNBS colitis Brain Res. 2009 1279 109 120 10.1016/j.brainres.2009.04.038 19406112 PMC2743074 · DOI
  62. [63]Liu M. Kay J.C. Shen S. Qiao L.-Y. Endogenous BDNF augments NMDA receptor phosphorylation in the spinal cord via PLCγ, PKC, and PI3K/Akt pathways during colitis J. Neuroinflamm. 2015 12 151 10.1186/s12974-015-0371-z PMC4545933 26289587 · DOI
  63. [64]Tan L.-H. Li K.-G. Wu Y.-Y. Guo M.-W. Lan Y. Wang S. Zhu W.-L. Ren X.-X. Effect of Electroacupuncture at Different Acupoints on the Expression of NMDA Receptors in ACC and Colon in IBS Rats Evid.-Based Complement. Altern. Med. 2019 2019 4213928 10.1155/2019/4213928 30854008 PMC6377955 · DOI
  64. [65]Kim M. Kim H. Kim H. Anti-Inflammatory Effect of Protopine through MAPK and NF-κB Signaling Regulation in HepG2 Cell Molecules 2022 27 4601 10.3390/molecules27144601 35889472 PMC9324321 · DOI
  65. [66]Kundu-Michalik S. Bisotti M.-A. Lipsius E. Bauche A. Kruppa A. Klokow T. Kammler G. Kruppa J. Nucleolar Binding Sequences of the Ribosomal Protein S6e Family Reside in Evolutionary Highly Conserved Peptide Clusters Mol. Biol. Evol. 2008 25 580 590 10.1093/molbev/msn002 18178970 · DOI
  66. [67]Kass-Simon G. Zompa M.A. Scappaticci A.A. Zackroff R.V. Hufnagel L.A. Nucleolar binding of an anti-NMDA receptor antibody in hydra: A non-canonical role for an NMDA receptor protein? J. Exp. Zool. Part A Ecol. Integr. Physiol. 2009 311 763 775 10.1002/jez.563 19658087 · DOI
  67. [68]Fan W. Xing Y. Zhong Y. Chen C. Shen Y. Expression of NMDA receptor subunit 1 in the rat retina Acta Histochem. 2013 115 42 47 10.1016/j.acthis.2012.03.005 22512920 · DOI
  68. [69]Ishimaru Y. Sumino A. Kajioka D. Shibagaki F. Yamamuro A. Yoshioka Y. Maeda S. Apelin protects against NMDA-induced retinal neuronal death via an APJ receptor by activating Akt and ERK1/2, and suppressing TNF-α expression in mice J. Pharmacol. Sci. 2017 133 34 41 10.1016/j.jphs.2016.12.002 28087150 · DOI
  69. [70]Del Caño G.G. Gerrikagoitia I. Sarasa M. Matute C. Martínez-Millán L. Ionotropic glutamate receptor subunits are differentially regulated in the motoneuronal pools of the rat hypoglossal nucleus in response to axotomy J. Neurocytol. 2000 29 509 523 10.1023/A:1007249829659 11279366 · DOI
  70. [71]Awobuluyi M. Lipton S.A. Sucher N.J. Translationally distinct populations of NMDA receptor subunit NR1 mRNA in the developing rat brain J. Neurochem. 2003 87 1066 1075 10.1046/j.1471-4159.2003.02048.x 14622087 · DOI
  71. [72]Irfan J. Febrianto M.R. Sharma A. Rose T. Mahmudzade Y. Di Giovanni S. Nagy I. Torres-Perez J.V. DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain Int. J. Mol. Sci. 2022 23 752 10.3390/ijms23020752 35054943 PMC8775747 · DOI
  72. [73]Loureiro C.M. Fachim H.A. Corsi-Zuelli F. Shuhama R. Joca S. Menezes P.R. Dalton C.F. Del-Ben C.M. Louzada-Junior P. Reynolds G.P. Epigenetic-mediated N-methyl-D-aspartate receptor changes in the brain of isolated reared rats Epigenomics 2020 12 1983 1997 10.2217/epi-2020-0151 33242253 · DOI
  73. [74]Guglietti B. Sivasankar S. Mustafa S. Corrigan F. Collins-Praino L.E. Fyn Kinase Activity and Its Role in Neurodegenerative Disease Pathology: A Potential Universal Target? Mol. Neurobiol. 2021 58 5986 6005 10.1007/s12035-021-02518-3 34432266 · DOI
  74. [75]Kostopoulou O.N. Wilhelmi V. Raiss S. Ananthaseshan S. Lindström M.S. Bartek J. Söderberg-Naucler C. Human cytomegalovirus and Herpes Simplex type I virus can engage RNA polymerase I for transcription of immediate early genes Oncotarget 2017 8 96536 96552 10.18632/oncotarget.22106 29228551 PMC5722503 · DOI
  75. [76]Lafita-Navarro M. Conacci-Sorrell M. Nucleolar stress: From development to cancer Semin. Cell Dev. Biol. 2023 136 64 74 10.1016/j.semcdb.2022.04.001 35410715 PMC9883801 · DOI
  76. [77]He J. Qin Z. Chen X. He W. Li D. Zhang L. Le Y. Xiong Q. Zhang B. Wang H. HIF-1α Ameliorates Diabetic Neuropathic Pain via Parkin-Mediated Mitophagy in a Mouse Model BioMed Res. Int. 2022 2022 1 18 10.1155/2022/5274375 PMC9398773 36017378 · DOI
  77. [78]Nazari-Khanamiri F. Ghasemnejad-Berenji M. Resveratrol may ameliorate rheumatoid arthritis via the STAT3/HIF-1/VEGF molecular pathway J. Food Biochem. 2022 46 e14182 10.1111/jfbc.14182 35415913 · DOI
  78. [79]Wang S. Lim G. Mao J. Sung B. Mao J. Regulation of the trigeminal NR1 subunit expression induced by inflammation of the temporomandibular joint region in rats Pain 2009 141 97 103 10.1016/j.pain.2008.10.021 19058915 PMC3491650 · DOI
  79. [80]Wang J. Sun Z. Wang Y. Wang H. Guo Y. The role and mechanism of glutamic NMDA receptor in the mechanical hyperalgesia in diabetic rats Neurol. Res. 2017 39 1006 1013 10.1080/01616412.2017.1364515 28814157 · DOI
  80. [81]Matos-Perdomo E. Machín F. Nucleolar and Ribosomal DNA Structure under Stress: Yeast Lessons for Aging and Cancer Cells 2019 8 779 10.3390/cells8080779 31357498 PMC6721496 · DOI
  81. [82]Chakraborty A. Murphy S. Coleman N. The Role of NMDA Receptors in Neural Stem Cell Proliferation and Differentiation Stem Cells Dev. 2017 26 798 807 10.1089/scd.2016.0325 28381110 · DOI
  82. [83]Sharma N.M. Cunningham C.J. Zheng H. Liu X. Patel K.P. Hypoxia-Inducible Factor-1α Mediates Increased Sympathoexcitation via Glutamatergic N-Methyl-d-Aspartate Receptors in the Paraventricular Nucleus of Rats with Chronic Heart Failure Circ. Heart Fail. 2016 9 e003423 10.1161/CIRCHEARTFAILURE.116.003423 27810863 PMC5123857 · DOI
  83. [84]Tong G. Takahashi H. Tu S. Shin Y. Talantova M. Zago W. Xia P. Nie Z. Goetz T. Zhang D. Modulation of NMDA Receptor Properties and Synaptic Transmission by the NR3A Subunit in Mouse Hippocampal and Cerebrocortical Neurons J. Neurophysiol. 2008 99 122 132 10.1152/jn.01044.2006 18003876 PMC4586267 · DOI
  84. [85]Hajdú T. Juhász T. Szűcs-Somogyi C. Rácz K. Zákány R. NR1 and NR3B Composed Intranuclear N-methyl-d-aspartate Receptor Complexes in Human Melanoma Cells Int. J. Mol. Sci. 2018 19 1929 10.3390/ijms19071929 29966365 PMC6073738 · DOI
  85. [86]Buchheit T. Van de Ven T. Shaw A. Epigenetics and the Transition from Acute to Chronic Pain Pain Med. 2012 13 1474 1490 10.1111/j.1526-4637.2012.01488.x 22978429 PMC3501579 · DOI
  86. [87]Biswal S. Das D. Barhwal K. Kumar A. Nag T.C. Thakur M.K. Hota S.K. Kumar B. Epigenetic Regulation of SNAP25 Prevents Progressive Glutamate Excitotoxicty in Hypoxic CA3 Neurons Mol. Neurobiol. 2017 54 6133 6147 10.1007/s12035-016-0156-0 27699604 · DOI
  87. [88]Vecino R. Burguete M.C. Jover-Mengual T. Agulla J. Bobo-Jiménez V. Salom J.B. Almeida A. Delgado-Esteban M. The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to ischemia Sci. Rep. 2018 8 1610 10.1038/s41598-018-19921-x 29371613 PMC5785500 · DOI
  88. [89]Noor S. Sanchez J.J. Vanderwall A.G. Sun M.S. Maxwell J.R. Davies S. Jantzie L.L. Petersen T.R. Savage D.D. Milligan E.D. Prenatal alcohol exposure potentiates chronic neuropathic pain, spinal glial and immune cell activation and alters sciatic nerve and DRG cytokine levels Brain Behav. Immun. 2017 61 80 95 10.1016/j.bbi.2016.12.016 28011263 PMC5316367 · DOI
  89. [90]Sanchez J.J. Sanchez J.E. Noor S. Ruffaner-Hanson C.D. Davies S. Wagner C.R. Jantzie L.L. Mellios N. Savage D.D. Milligan E.D. Targeting the β2-integrin LFA-1, reduces adverse neuroimmune actions in neuropathic susceptibility caused by prenatal alcohol exposure Acta Neuropathol. Commun. 2019 7 54 10.1186/s40478-019-0701-y 30961664 PMC6454692 · DOI
  90. [91]Sarantis K. Antoniou K. Matsokis N. Angelatou F. Exposure to novel environment is characterized by an interaction of D1/NMDA receptors underlined by phosphorylation of the NMDA and AMPA receptor subunits and activation of ERK1/2 signaling, leading to epigenetic changes and gene expression in rat hippocampus Neurochem. Int. 2012 60 55 67 10.1016/j.neuint.2011.10.018 22080157 · DOI
  91. [92]Stover J.F. Sakowitz O.W. Kroppenstedt S.N. Thomale U.W. Kempski O.S. Unterberg A.W. Flügge G. Differential effects of prolonged isoflurane anesthesia on plasma, extracellular, and CSF glutamate, neuronal activity, 125I-Mk801 NMDA receptor binding, and brain edema in traumatic brain-injured rats Acta Neurochir. 2004 146 819 830 10.1007/s00701-004-0281-9 15254804 · DOI
  92. [93]Jiang X. Tian F. Mearow K. Okagaki P. Lipsky R.H. The excitoprotective effect of N-methyl-d-aspartate receptors is mediated by a brain-derived neurotrophic factor autocrine loop in cultured hippocampal neurons J. Neurochem. 2005 94 713 722 10.1111/j.1471-4159.2005.03200.x 16000165 · DOI
  93. [94]Xu H.-N. Li L.-X. Wang Y.-X. Wang H.-G. An D. Heng B. Liu Y.-Q. Genistein inhibits Aβ25–35-induced SH-SY5Y cell damage by modulating the expression of apoptosis-related proteins and Ca2+ influx through ionotropic glutamate receptors Phytother. Res. 2019 33 431 441 10.1002/ptr.6239 30450837 · DOI
  94. [95]McNearney T. Baethge B.A. Cao S. Alam R. Lisse J.R. Westlund K.N. Excitatory amino acids, TNF-α, and chemokine levels in synovial fluids of patients with active arthropathies Clin. Exp. Immunol. 2004 137 621 627 10.1111/j.1365-2249.2004.02563.x 15320917 PMC1809131 · DOI
  95. [96]Genever P.G. Maxfield S.J. Skerry T.M. Kennovin G.D. Maltman J. Bowgen C.J. Raxworthy M.J. Evidence for a Novel Glutamate-Mediated Signaling Pathway in Keratinocytes J. Investig. Dermatol. 1999 112 337 342 10.1046/j.1523-1747.1999.00509.x 10084312 · DOI
  96. [97]Liu L. Yang T. Simon S.A. The protein tyrosine kinase inhibitor, genistein, decreases excitability of nociceptive neurons Pain 2004 112 131 141 10.1016/j.pain.2004.08.005 15494193 · DOI

Cited by

Sorted by citations

Authors
McNearney, T. A., & Westlund, K. N.
Affiliations
  • The University of Texas Medical Branch at Galveston (US)
  • University of New Mexico (US)
Corresponding author
Westlund, Karin N.
ORCID
Westlund, Karin N.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2023-08-25
Volume
24
Issue
17
Pages
13196
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms241713196
PMC
PMC10488196
OpenAlex
W4386162009
Cited by
9
References
1
Citations by year
2026: 4 · 2025: 2 · 2024: 2 · 2023: 1
FWCI
0.35
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Sealy Endowment (NS32778, NS11255, AR48371 AR48371, BX002695)
  • NIH (NS32778, NS11255, AR48371 AR48371, BX002695)
  • P01 (NS32778, NS11255, AR48371 AR48371, BX002695)
  • R21 (NS32778, NS11255, AR48371 AR48371, BX002695)
  • Dana Foundation (NS32778, NS11255, AR48371 AR48371, BX002695)
  • anonymous UTMB endowment (NS32778, NS11255, AR48371 AR48371, BX002695)
  • Merit Review Award (NS32778, NS11255, AR48371 AR48371, BX002695)
  • Office of Research and Development, Medical Research Service, United States Department of Veterans Affairs (NS32778, NS11255, AR48371 AR48371, BX002695)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
GluN1, NMDA receptor 1, nuclear translocation, nociception, pain, glutamate receptors, subnuclear localization, nucleolus, immediate early genes, excitotoxicity, long-term potentiation, receptor heterodimerization, intracellular trafficking
MeSH terms
Cell Nucleus, Humans, Nerve Tissue Proteins, Pain, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Excitatory Amino Acid Agonists, Nociception

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