CoChat
Sign Up
Cited by 730Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchTryptophan and brain disorders

Tumor necrosis factor alpha: A link between neuroinflammation and excitotoxicity

Open access
Olmos, Gabriel, Lladó, Jerònia·2014·Mediators of Inflammation
DOI 10.1155/2014/861231PMC PMC4055424
Open this paper in CoChat — free accountOpen PDF

Abstract

Tumor necrosis factor alpha (TNF- α ) is a proinflammatory cytokine that exerts both homeostatic and pathophysiological roles in the central nervous system. In pathological conditions, microglia release large amounts of TNF- α ; this de novo production of TNF- α is an important component of the so-called neuroinflammatory response that is associated with several neurological disorders. In addition, TNF- α can potentiate glutamate-mediated cytotoxicity by two complementary mechanisms: indirectly, by inhibiting glutamate transport on astrocytes, and directly, by rapidly triggering the surface expression of Ca +2 permeable-AMPA receptors and NMDA receptors, while decreasing inhibitory GABA A receptors on neurons. Thus, the net effect of TNF- α is to alter the balance of excitation and inhibition resulting in a higher synaptic excitatory/inhibitory ratio. This review summarizes the current knowledge of the cellular and molecular mechanisms by which TNF- α links the neuroinflammatory and excitotoxic processes that occur in several neurodegenerative diseases, but with a special emphasis on amyotrophic lateral sclerosis (ALS). As microglial activation and upregulation of TNF- α expression is a common feature of several CNS diseases, as well as chronic opioid exposure and neuropathic pain, modulating TNF- α signaling may represent a valuable target for intervention.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1155/2014/861231

Cites

9 of 9 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • TNFα is expressed in neurons during neuroinflammation.

    “Further study is needed to confirm whether this also occurs in neurons; however, it is clear that TNFα is expressed in neurons during neuroinflammation [43].”

    From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [43]

  • TNF-α can potentiate glutamate-mediated cytotoxicity by indirectly inhibiting glutamate transport on astrocytes and directly stimulating microglial and/or astrocyte glutamate release in an autocrine manner.

    “For instance, TNF-α can potentiate glutamate-mediated cytotoxicity by two complementary mechanisms: indirectly, by inhibiting glutamate transport on astrocytes, and directly, by stimulating extensive microglial and/or astrocyte glutamate release in an autocrine manner.”

    From TNF-alpha-induced microglia activation requires miR-342: Impact on NF-kB signaling and neurotoxicity (2020) · cites this paper as [37]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 141

  1. [2]Clark IA How TNF was recognized as a key mechanism of disease Cytokine and Growth Factor Reviews 2007 18 3-4 335 343 2-s2.0-34250014777 17493863
  2. [3]Montgomery SL Bowers WJ Tumor necrosis factor-alpha and the roles it plays in homeostatic and degenerative processes within the central nervous system Jounal of Neuroimmune Pharmacology 2012 7 1 42 59 21728035
  3. [4]Santello M Volterra A TNFalpha in synaptic function: switching gears Trends in Neurosciences 2012 35 10 638 647 22749718
  4. [6]Kaneko M Stellwagen D Malenka RC Stryker MP Tumor necrosis factor-α mediates one component of competitive, experience-dependent plasticity in developing visual cortex Neuron 2008 58 5 673 680 2-s2.0-44649093265 18549780 PMC2884387
  5. [7]Baune BT Wiede F Braun A Golledge J Arolt V Koerner H Cognitive dysfunction in mice deficient for TNF- and its receptors American Journal of Medical Genetics B: Neuropsychiatric Genetics 2008 147 7 1056 1064 2-s2.0-55349145652 18286589
  6. [8]Beste C Baune BT Falkenstein M Konrad C Variations in the TNF-α gene (TNF-α -308G→A) affect attention and action selection mechanisms in a dissociated fashion Journal of Neurophysiology 2010 104 5 2523 2531 2-s2.0-78049494400 20810691
  7. [10]Plata-Salamán CR Cytokines and feeding International Journal of Obesity 2001 25 supplement 5 S48 S52 2-s2.0-0035711225 11840215
  8. [11]Santello M Bezzi P Volterra A TNFα controls glutamatergic gliotransmission in the hippocampal dentate gyrus Neuron 2011 69 5 988 1001 2-s2.0-79952234841 21382557
  9. [12]McCoy MK Tansey MG TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease Journal of Neuroinflammation 2008 5 article 45 2-s2.0-55949104665 PMC2577641 18925972
  10. [13]Frankola KA Greig NH Luo W Tweedie D Targeting TNF-alpha to elucidate and ameliorate neuroinflammation in neurodegenerative diseases CNS and Neurological Disorders—Drug Targets 2011 10 3 391 403 2-s2.0-79951701971 21288189 PMC4663975
  11. [14]Wyss-Coray T Mucke L Inflammation in neurodegenerative disease—a double-edged sword Neuron 2002 35 3 419 432 2-s2.0-0036685522 12165466
  12. [15]Pickering M Cumiskey D O’Connor JJ Actions of TNF-α on glutamatergic synaptic transmission in the central nervous system Experimental Physiology 2005 90 5 663 670 2-s2.0-26044438460 15944202
  13. [16]Goodman JC Robertson CS Grossman RG Narayan RK Elevation of tumor necrosis factor in head injury Journal of Neuroimmunology 1990 30 2-3 213 217 2-s2.0-0025096198 2229409
  14. [17]Liu T Clark RK McDonnell PC Tumor necrosis factor-α expression in ischemic neurons Stroke 1994 25 7 1481 1488 2-s2.0-0028292231 8023366
  15. [18]Feuerstein GZ Liu T Barone FC Cytokines, inflammation, and brain injury: role of tumor necrosis factor-alpha Cerebrovascular and Brain Metabolism Reviews 1994 6 4 341 360 2-s2.0-0028675999 7880718
  16. [19]Fillit H Ding W Buee L Elevated circulating tumor necrosis factor levels in Alzheimer’s disease Neuroscience Letters 1991 129 2 318 320 2-s2.0-0025807206 1745413
  17. [20]Álvarez A Cacabelos R Sanpedro C García-Fantini M Aleixandre M Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease Neurobiology of Aging 2007 28 4 533 536 2-s2.0-33847140273 16569464
  18. [21]Boka G Anglade P Wallach D Javoy-Agid F Agid Y Hirsch EC Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson’s disease Neuroscience Letters 1994 172 1-2 151 154 2-s2.0-0028364696 8084523
  19. [22]Mogi M Harada M Riederer P Narabayashi H Fujita K Nagatsu T Tumor necrosis factor-α (TNF-α) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients Neuroscience Letters 1994 165 1-2 208 210 2-s2.0-0028178281 8015728
  20. [23]Sharief MK Hentges R Association between tumor necrosis factor-α and disease progression in patients with multiple sclerosis The New England Journal of Medicine 1991 325 7 467 472 2-s2.0-0025773147 1852181
  21. [24]Rieckmann P Albrecht M Kitze B Tumor necrosis factor-α messenger RNA expression in patients with relapsing-remitting multiple sclerosis is associated with disease activity Annals of Neurology 1995 37 1 82 88 2-s2.0-0028985320 7818262
  22. [25]Poloni M Facchetti D Mai R Circulating levels of tumour necrosis factor-α and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis Neuroscience Letters 2000 287 3 211 214 2-s2.0-0034733968 10863032
  23. [26]Babu GN Kumar A Chandra R Puri SK Kalita J Misra UK Elevated inflammatory markers in a group of amyotrophic lateral sclerosis patients from northern India Neurochemical Research 2008 33 6 1145 1149 2-s2.0-42149154856 18246426
  24. [27]Idriss HT Naismith JH TNF alpha and the TNF receptor superfamily: structure-function relationship(s) Microscopy Research and Technique 2000 50 3 184 195 10891884
  25. [29]Tartaglia LA Goeddel DV Two TNF receptors Immunology Today 1992 13 5 151 153 2-s2.0-0026514526 1322675
  26. [30]Depuydt B van Loo G Vandenabeele P Declercq W Induction of apoptosis by TNF receptor 2 in a T-cell hybridoma is FADD dependent and blocked by caspase-8 inhibitors Journal of Cell Science 2005 118 part 3 497 504 2-s2.0-14644414800 15657078
  27. [31]Chen G Goeddel DV TNF-R1 signaling: a beautiful pathway Science 2002 296 5573 1634 1635 2-s2.0-0037204948 12040173
  28. [32]Liu Z-G Han J Cellular responses to tumor necrosis factor Current Issues in Molecular Biology 2001 3 4 79 90 2-s2.0-0035157953 11719971
  29. [33]Wajant H Pfizenmaier K Scheurich P Tumor necrosis factor signaling Cell Death and Differentiation 2003 10 1 45 65 2-s2.0-0037276438 12655295
  30. [34]Chung IY Benveniste EN Tumor necrosis factor-α production by astrocytes. Induction by lipopolysaccharide, IFN-γ, and IL-1β Journal of Immunology 1990 144 8 2999 3007 2-s2.0-0025304816 2109008
  31. [35]Gahring LC Carlson NG Kulmar RA Rogers SW Neuronal expression of tumor necrosis factor alpha in the murine brain Neuroimmunomodulation 1996 3 5 289 303 9218250
  32. [36]Breder CD Tsujimoto M Terano Y Scott DW Saper CB Distribution and characterization of tumor necrosis factor-α-like immunoreactivity in the murine central nervous system Journal of Comparative Neurology 1993 337 4 543 567 2-s2.0-0027483753 8288770
  33. [37]Welser-Alves JV Milner R Microglia are the major source of TNF-alpha and TGF-beta1 in postnatal glial cultures, regulation by cytokines, lipopolysaccharide, and vitronectin Neurochemistry International 2013 63 1 47 53 23619393 PMC3819935
  34. [39]Nguyen VT Benveniste EN Critical role of tumor necrosis factor-α and NF-κB in interferon-γ-induced CD40 expression in microglia/macrophages The Journal of Biological Chemistry 2002 277 16 13796 13803 2-s2.0-0037134429 11830590
  35. [40]Mangano EN Litteljohn D So R Interferon-gamma plays a role in paraquat-induced neurodegeneration involving oxidative and proinflammatory pathways Neurobiology of Aging 2012 33 7 1411 1426 21482445
  36. [41]Frei K Siepl C Groscurth P Bodmer S Schwerdel C Fontana A Antigen presentation and tumor cytotoxicity by interferon-γ-treated microglial cells European Journal of Immunology 1987 17 9 1271 1278 2-s2.0-0023618311 3115791
  37. [42]Harms AS Cao S Rowse AL MHCII is required for alpha-synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration The Journal of Neuroscience 2013 33 23 9592 9600 23739956 PMC3903980
  38. [43]Byun K Young Kim J Bayarsaikhan E Quantitative proteomic analysis reveals that lipopolysaccharide induces mitogen-activated protein kinase-dependent activation in human microglial cells Electrophoresis 2012 33 24 3756 3763 23161002
  39. [44]Kim BW Koppula S Hong SS Regulation of microglia activity by glaucocalyxin-A: attenuation of lipopolysaccharide-stimulated neuroinflammation through NF-kappaB and p38 MAPK signaling pathways PLoS ONE 2013 8 2 e55792 PMC3564949 23393601
  40. [45]Pangestuti R Bak S-S Kim S-K Attenuation of pro-inflammatory mediators in LPS-stimulated BV2 microglia by chitooligosaccharides via the MAPK signaling pathway International Journal of Biological Macromolecules 2011 49 4 599 606 2-s2.0-80052293126 21704648
  41. [46]Zhao S Zhang L Lian G Sildenafil attenuates LPS-induced pro-inflammatory responses through down-regulation of intracellular ROS-related MAPK/NF-κB signaling pathways in N9 microglia International Immunopharmacology 2011 11 4 468 474 2-s2.0-79952736802 21220057
  42. [47]Mir M Tolosa L Asensio VJ Lladó J Olmos G Complementary roles of tumor necrosis factor alpha and interferon gamma in inducible microglial nitric oxide generation Journal of Neuroimmunology 2008 204 1-2 101 109 2-s2.0-54849410809 18703234
  43. [48]Guha M O’Connell MA Pawlinski R Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor α expression by inducing Elk-1 phosphorylation and Egr-1 expression Blood 2001 98 5 1429 1439 2-s2.0-0035469890 11520792
  44. [49]Young HA Hardy KJ Role of interferon-γ in immune cell regulation Journal of Leukocyte Biology 1995 58 4 373 381 2-s2.0-0028848472 7561512
  45. [50]Aloisi F Serafini B Adorini L Glia-T cell dialogue Journal of Neuroimmunology 2000 107 2 111 117 2-s2.0-0034710339 10854644
  46. [51]Hickey WF Hsu BL Kimura H T-lymphocyte entry into the central nervous system Journal of Neuroscience Research 1991 28 2 254 260 2-s2.0-0025981021 2033653
  47. [52]Archambault AS Sim J Gimenez MAT Russell JH Defining antigen-dependent stages of T cell migration from the blood to the central nervous system parenchyma European Journal of Immunology 2005 35 4 1076 1085 2-s2.0-17444382009 15761850
  48. [53]Ransohoff RM Engelhardt B The anatomical and cellular basis of immune surveillance in the central nervous system Nature Reviews Immunolology 2012 12 9 623 635 22903150
  49. [54]Merrill JE Benveniste EN Cytokines in inflammatory brain lesions: helpful and harmful Trends in Neurosciences 1996 19 8 331 338 8843602
  50. [55]Wekerle H Sun D Oropeza-Wekerle RL Meyermann R Immune reactivity in the nervous system: modulation of T-lymphocyte activation by glial cells Journal of Experimental Biology 1987 132 43 57 2-s2.0-0023413923 3323405
  51. [56]Appel SH CD4+ T cells mediate cytotoxicity in neurodegenerative diseases The Journal of Clinical Investigation 2009 119 1 13 15 2-s2.0-61749097003 19104142 PMC2613473
  52. [57]Troost D van den Oord JJ de Jong JMBV Swaab DF Lymphocytic infiltration in the spinal cord of patients with amyotrophic lateral sclerosis Clinical Neuropathology 1989 8 6 289 294 2-s2.0-0024955336 2533530
  53. [58]Brochard V Combadière B Prigent A Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease The Journal of Clinical Investigation 2009 119 1 182 192 2-s2.0-58849107919 19104149 PMC2613467
  54. [59]Medana I Martinic MA Wekerle H Neumann H Transection of major histocompatibility complex class I-induced neurites by cytotoxic T lymphocytes The American Journal of Pathology 2001 159 3 809 815 2-s2.0-0034842960 11549572 PMC1850471
  55. [60]Hohlfeld R Kerschensteiner M Stadelmann C Lassmann H Wekerle H The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis Journal of Neuroimmunology 2000 107 2 161 166 2-s2.0-0034710340 10854651
  56. [61]Schwartz M Cohen I Lazarov-Spiegler O Moalem G Yoles E The remedy may lie in ourselves: prospects for immune cell therapy in central nervous system protection and repair Journal of Molecular Medicine 1999 77 10 713 717 2-s2.0-0032706594 10606206
  57. [62]Beers DR Henkel JS Zhao W Wang J Appel SH CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS Proceedings of the National Academy of Sciences of the United States of America 2008 105 40 15558 15563 2-s2.0-55749110043 18809917 PMC2547419
  58. [63]Chiu IM Chen A Zheng Y T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS Proceedings of the National Academy of Sciences of the United States of America 2008 105 46 17913 17918 2-s2.0-56649100689 18997009 PMC2581614
  59. [64]Liu B Hong J-S Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention Journal of Pharmacology and Experimental Therapeutics 2003 304 1 1 7 2-s2.0-0037215645 12490568
  60. [66]Mir M Asensio VJ Tolosa L Tumor necrosis factor alpha and interferon gamma cooperatively induce oxidative stress and motoneuron death in rat spinal cord embryonic explants Neuroscience 2009 162 4 959 971 2-s2.0-67949100439 19477238
  61. [67]Watkins JC Evans RH Excitatory amino acid transmitters Annual Review of Pharmacology and Toxicology 1981 21 165 204 2-s2.0-0019401318 6112965
  62. [68]Olney JW McGeer EG Olney JW McGeer PL Neurotoxicity of excitatory amino acids Kainic Acid as a Tool in Neurobiology 1978 New York, NY, USA Raven Press 95 112
  63. [69]Doble A The role of excitotoxicity in neurodegenerative disease: implications for therapy Pharmacology and Therapeutics 1999 81 3 163 221 2-s2.0-0032967382 10334661
  64. [70]Gelbard HA Dzenko KA DiLoreto D del Cerro C del Cerro M Epstein LG Neurotoxic effects of tumor necrosis factor alpha in primary human neuronal cultures are mediated by activation of the glutamate AMPA receptor subtype: implications for AIDS neuropathogenesis Developmental Neuroscience 1993 15 6 417 422 2-s2.0-0027767445 7835247
  65. [71]Chao CC Hu S Tumor necrosis factor-alpha potentiates glutamate neurotoxicity in human fetal brain cell cultures Developmental Neuroscience 1994 16 3-4 172 179 2-s2.0-0028577356 7705222
  66. [72]Hermann GE Rogers RC Bresnahan JC Beattie MS Tumor necrosis factor-α induces cFOS and strongly potentiates glutamate-mediated cell death in the rat spinal cord Neurobiology of Disease 2001 8 4 590 599 2-s2.0-0034877451 11493024
  67. [73]Takeuchi H Jin S Wang J Tumor necrosis factor-α induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner The Journal of Biological Chemistry 2006 281 30 21362 21368 2-s2.0-33746354022 16720574
  68. [74]Taylor DL Jones F Chen Seho Kubota ESF Pocock JM Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necrosis factor α-induced neurotoxicity in concert with microglial-derived Fas ligand The Journal of Neuroscience 2005 25 11 2952 2964 2-s2.0-15244350494 15772355 PMC6725132
  69. [75]Zhu W Zheng H Shao X Wang W Yao Q Li Z Excitotoxicity of TNFα derived from KA activated microglia on hippocampal neurons in vitro and in vivo Journal of Neurochemistry 2010 114 2 386 396 2-s2.0-77953845018 20438614
  70. [76]Kuno R Wang J Kawanokuchi J Takeuchi H Mizuno T Suzumura A Autocrine activation of microglia by tumor necrosis factor-α Journal of Neuroimmunology 2005 162 1-2 89 96 2-s2.0-17044396389 15833363
  71. [77]Bezzi P Domercq M Brambilla L CXCR4-activated astrocyte glutamate release via TNFa: amplification by microglia triggers neurotoxicity Nature Neuroscience 2001 4 7 702 710 2-s2.0-0034960228 11426226
  72. [78]Bezzi P Carmignoto G Pasti L Prostaglandins stimulate calcium-dependent glutamate release in astrocytes Nature 1998 391 6664 281 285 2-s2.0-0032518514 9440691
  73. [79]Gegelashvili G Schousboe A High affinity glutamate transporters: regulation of expression and activity Molecular Pharmacology 1997 52 1 6 15 9224806
  74. [80]Zhou Y Danbolt NC GABA and glutamate transporters in brain Frontiers in Endocrinology 2013 4 165 PMC3822327 24273530
  75. [81]Tilleux S Hermans E Neuroinflammation and regulation of glial glutamate uptake in neurological disorders Journal of Neuroscience Research 2007 85 10 2059 2070 2-s2.0-34547435817 17497670
  76. [82]Danbolt NC Purification and reconstitution of the sodium- and potassium-coupled glutamate transport glycoprotein from rat brain Biochemistry 1990 29 28 6734 6740 2-s2.0-0025316950 1697765
  77. [83]Danbolt NC Glutamate uptake Progress in Neurobiology 2001 65 1 1 105 2-s2.0-0035001341 11369436
  78. [84]Sitcheran R Gupta P Fisher PB Baldwin AS Positive and negative regulation of EAAT2 by NF-κB: a role for N-myc in TNFα-controlled repression The EMBO Journal 2005 24 3 510 520 2-s2.0-14844316278 15660126 PMC548660
  79. [85]Wang Z Pekarskaya O Bencheikh M Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120 Virology 2003 312 1 60 73 2-s2.0-0012450945 12890621
  80. [86]Tolosa L Caraballo-Miralles V Olmos G Lladó J TNF-α potentiates glutamate-induced spinal cord motoneuron death via NF-κB Molecular and Cellular Neuroscience 2011 46 1 176 186 2-s2.0-78650869541 20849956
  81. [87]Zou JY Crews FT TNFα potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NFκB inhibition Brain Research 2005 1034 1-2 11 24 2-s2.0-13844270562 15713255
  82. [88]Hensley K Mhatre M Mou S On the relation of oxidative stress to neuroinflammation: lessons learned from the G93A-SOD1 mouse model of amyotrophic lateral sclerosis Antioxidants & Redox Signaling 2006 8 11-12 2075 2087 2-s2.0-33947640544 17034351
  83. [89]Mhatrea M Floyd RA Hensley K Oxidative stress and neuroinflammation in Alzheimer’s disease and amyotrophic lateral sclerosis: common links and potential therapeutic targets Journal of Alzheimer’s Disease 2004 6 2 147 157 2-s2.0-2342417953 15096698
  84. [90]Trotti D Danbolt NC Volterra A Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration? Trends in Pharmacological Sciences 1998 19 8 328 334 2-s2.0-0032145886 9745361
  85. [91]Miralles VJ Martínez-López I Zaragozá R Na+ dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) in primary astrocyte cultures: effect of oxidative stress Brain Research 2001 922 1 21 29 2-s2.0-0035856880 11730698
  86. [92]Rao SD Yin HZ Weiss JH Disruption of glial glutamate transport by reactive oxygen species produced in motor neurons Journal of Neuroscience 2003 23 7 2627 2633 2-s2.0-0345269737 12684448 PMC6742077
  87. [93]Pasinelli P Houseweart MK Brown RH Jr. Cleveland DW Caspase-1 and -3 are sequentially activated in motor neuron death in Cu,Zn superoxide dismutase-mediated familial amyotrophic lateral sclerosis Proceedings of the National Academy of Sciences of the United States of America 2000 97 25 13901 13906 2-s2.0-0034610328 11095709 PMC17673
  88. [94]Boston-Howes W Gibb SL Williams EO Pasinelli P Brown RH Jr. Trotti D Caspase-3 cleaves and inactivates the glutamate transporter EAAT2 The Journal of Biological Chemistry 2006 281 20 14076 14084 2-s2.0-33744909882 16567804
  89. [95]van den Bosch L van Damme P Bogaert E Robberecht W The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis Biochimica et Biophysica Acta 2006 1762 11-12 1068 1082 2-s2.0-33751229311 16806844
  90. [96]Rothstein JD van Kammen M Levey AI Martin LJ Kuncl RW Selective loss of glial glutamate transporter GLT-1 amyotrophic lateral sclerosis Annals of Neurology 1995 38 1 73 84 2-s2.0-0029030610 7611729
  91. [98]Howland DS Liu J She Y Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS) Proceedings of the National Academy of Sciences of the United States of America 2002 99 3 1604 1609 2-s2.0-0037022339 11818550 PMC122237
  92. [99]Shobha K Vijayalakshmi K Alladi PA Nalini A Sathyaprabha TN Raju TR Altered in-vitro and in-vivo expression of glial glutamate transporter-1 following exposure to cerebrospinal fluid of amyotrophic lateral sclerosis patients Journal of the Neurological Sciences 2007 254 1-2 9 16 2-s2.0-33847330077 17254611
  93. [100]Nakanishi S Molecular diversity of glutamate receptors and implications for brain function Science 1992 258 5082 597 603 2-s2.0-0026437728 1329206
  94. [101]Seeburg PH The TINS/TiPS lecture: the molecular biology of mammalian glutamate receptor channels Trends in Neurosciences 1993 16 9 359 365 2-s2.0-0027234701 7694406
  95. [102]Shi S-H Hayashi Y Esteban JA Malinow R Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons Cell 2001 105 3 331 343 2-s2.0-0035805143 11348590
  96. [103]Beattie MS Ferguson AR Bresnahan JC AMPA-receptor trafficking and injury-induced cell death The European Journal of Neuroscience 2010 32 2 290 297 2-s2.0-78951473274 20646045 PMC3032583
  97. [104]Turrigiano GG The self-tuning neuron: synaptic scaling of excitatory synapses Cell 2008 135 3 422 435 2-s2.0-54549125798 18984155 PMC2834419
  98. [105]Hollmann M Hartley M Heinemann S Ca2+ permeability of KA-AMPA—gated glutamate receptor channels depends on subunit composition Science 1991 252 5007 851 853 2-s2.0-0025923461 1709304
  99. [106]Verdoorn TA Burnashev N Monyer H Seeburg PH Sakmann B Structural determinants of ion flow through recombinant glutamate receptor channels Science 1991 252 5013 1715 1718 2-s2.0-0025879427 1710829
  100. [107]Pellegrini-Giampietro DE Gorter JA Bennett MV Zukin RS The GluR2 (GluR-B) hypothesis: Ca2+-permeable AMPA receptors in neurological disorders Trends in Neurosciences 1997 20 10 464 470 9347614
  101. [108]Weiss JH Sensi SL Ca2+-Zn2+ permeable AMPA or kainate receptors: possible key factors in selective neurodegeneration Trends in Neurosciences 2000 23 8 365 371 2-s2.0-0034238089 10906800
  102. [109]Yu Z Cheng G Wen X Wu GD Lee W-T Pleasure D Tumor necrosis factor α increases neuronal vulnerability to excitotoxic necrosis by inducing expression of the AMPA-glutamate receptor subunit GluR1 via an acid sphingomyelinase-and NF-κB-dependent mechanism Neurobiology of Disease 2002 11 1 199 213 2-s2.0-0036449523 12460558
  103. [110]Bernardino L Xapelli S Silva AP Modulator effects of interleukin-1β and tumor necrosis factor-α on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures The Journal of Neuroscience 2005 25 29 6734 6744 2-s2.0-22544483518 16033883 PMC6725352
  104. [112]Leonoudakis D Zhao P Beattie EC Rapid tumor necrosis factor α-induced exocytosis of glutamate receptor 2-lacking AMPA receptors to extrasynaptic plasma membrane potentiates excitotoxicity The Journal of Neuroscience 2008 28 9 2119 2130 2-s2.0-39849101377 18305246 PMC6671833
  105. [113]Ogoshi F Yin HZ Kuppumbatti Y Song B Amindari S Weiss JH Tumor necrosis-factor-alpha (TNF-α) induces rapid insertion of Ca2+-permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole- propionate (AMPA)/kainate (Ca-A/K) channels in a subset of hippocampal pyramidal neurons Experimental Neurology 2005 193 2 384 393 2-s2.0-18144394715 15869941
  106. [114]Ferguson AR Christensen RN Gensel JC Cell death after spinal cord injury is exacerbated by rapid TNFα-induced trafficking of GluR2-lacking AMPARs to the plasma membrane The Journal of Neuroscience 2008 28 44 11391 11400 2-s2.0-56149092503 18971481 PMC2598739
  107. [115]Han P Whelan PJ Tumor necrosis factor alpha enhances glutamatergic transmission onto spinal motoneurons Journal of Neurotrauma 2010 27 1 287 292 2-s2.0-76349125110 19811092
  108. [116]Rainey-Smith SR Andersson DA Williams RJ Rattray M Tumour necrosis factor alpha induces rapid reduction in AMPA receptor-mediated calcium entry in motor neurones by increasing cell surface expression of the GluR2 subunit: relevance to neurodegeneration Journal of Neurochemistry 2010 113 3 692 703 2-s2.0-77950633637 20132465
  109. [117]Williams TL Day NC Ince PG Kamboj RK Shaw PJ Calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors: a molecular determinant of selective vulnerability in amyotrophic lateral sclerosis Annals of Neurology 1997 42 2 200 207 9266730
  110. [118]Yin HZ Tang DT Weiss JH Intrathecal infusion of a Ca2+-permeable AMPA channel blocker slows loss of both motor neurons and of the astrocyte glutamate transporter, GLT-1 in a mutant SOD1 rat model of ALS Experimental Neurology 2007 207 2 177 185 2-s2.0-34548752918 17719032 PMC2083564
  111. [119]Tateno M Sadakata H Tanaka M Calcium-permeable AMPA receptors promote misfolding of mutant SOD1 protein and development of amyotrophic lateral sclerosis in a transgenic mouse model Human Molecular Genetics 2004 13 19 2183 2196 2-s2.0-5444222849 15294873
  112. [120]Corona JC Tapia R Ca2+-permeable AMPA receptors and intracellular Ca2+ determine motoneuron vulnerability in rat spinal cord in vivo Neuropharmacology 2007 52 5 1219 1228 2-s2.0-34047131622 17320918
  113. [121]Sargsyan SA Monk PN Shaw PJ Microglia as potential contributors to motor neuron injury in amyotrophic lateral sclerosis Glia 2005 51 4 241 253 2-s2.0-25444522220 15846792
  114. [122]Barbeito LH Pehar M Cassina P A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis Brain Research Reviews 2004 47 1–3 263 274 2-s2.0-9644255989 15572176
  115. [123]Tweedie D Sambamurti K Greig NH TNF-α inhibition as a treatment strategy for neurodegenerative disorders: new drug candidates and targets Current Alzheimer Research 2007 4 4 378 385 2-s2.0-34548726106 17908040
  116. [124]Yin HZ Hsu CI Yu S Rao SD Sorkin LS Weiss JH TNF-alpha triggers rapid membrane insertion of Ca2+ permeable AMPA receptors into adult motor neurons and enhances their susceptibility to slow excitotoxic injury Experimental Neurology 2012 238 2 93 102 22921461 PMC3498614
  117. [125]Llado J Tolosa L Olmos G Cellular and molecular mechanisms involved in the neuroprotective effects of VEGF on motoneurons Frontiers in Cellular Neuroscience 2013 7 181 PMC3803143 24155688
  118. [126]Bogaert E van Damme P Poesen K VEGF protects motor neurons against excitotoxicity by upregulation of GluR2 Neurobiology of Aging 2010 31 12 2185 2191 2-s2.0-77953732352 19185395
  119. [127]Wheeler D Knapp E Bandaru VVR Tumor necrosis factor-α-induced neutral sphingomyelinase-2 modulates synaptic plasticity by controlling the membrane insertion of NMDA receptors Journal of Neurochemistry 2009 109 5 1237 1249 2-s2.0-65549128703 19476542 PMC2688711
  120. [128]Floden AM Li S Combs CK β-Amyloid-stimulated microglia induce neuron death via synergistic stimulation of tumor necrosis factor α and NMDA receptors The Journal of Neuroscience 2005 25 10 2566 2575 2-s2.0-14944385354 15758166 PMC6725188
  121. [129]Stück ED Christensen RN Huie JR Tumor necrosis factor alpha mediates GABAA receptor trafficking to the plasma membrane of spinal cord neurons in vivo Neural Plasticity 2012 2012 2-s2.0-84859721983 261345 PMC3317039 22530155
  122. [130]Ferguson AR Washburn SN Crown ED Grau JW GABAA receptor activation is involved in noncontingent shock inhibition of instrumental conditioning in spinal rats Behavioral Neuroscience 2003 117 4 799 812 2-s2.0-0043167887 12931964
  123. [131]Huie JR Baumbauer KM Lee KH Glial tumor necrosis factor alpha (TNFalpha) generates metaplastic inhibition of spinal learning PLoS ONE 2012 7 6 e39751 PMC3379985 22745823
  124. [132]Pribiag H Stellwagen D TNF-alpha downregulates inhibitory neurotransmission through protein phosphatase 1-dependent trafficking of GABAA receptors The Journal of Neuroscience 2013 33 40 15879 15893 24089494 PMC6618471
  125. [133]Rubenstein JLR Merzenich MM Model of autism: increased ratio of excitation/inhibition in key neural systems Genes, Brain and Behavior 2003 2 5 255 267 2-s2.0-0242291090 PMC6748642 14606691
  126. [134]Yizhar O Fenno LE Prigge M Neocortical excitation/inhibition balance in information processing and social dysfunction Nature 2011 477 7363 171 178 2-s2.0-80052563319 21796121 PMC4155501
  127. [136]Wen Y-R Tan P-H Cheng J-K Liu Y-C Ji R-R Microglia: a promising target for treating neuropathic and postoperative pain, and morphine tolerance Journal of the Formosan Medical Association 2011 110 8 487 494 2-s2.0-79960807502 21783017 PMC3169792
  128. [137]Shen C-H Tsai R-Y Wong C-S Role of neuroinflammation in morphine tolerance: effect of tumor necrosis factor-alpha Acta Anaesthesiologica Taiwanica 2012 50 4 178 182 23385041
  129. [138]Shen C-H Tsai R-Y Shih M-S Etanercept restores the antinociceptive effect of morphine and suppresses spinal neuroinflammation in morphine-tolerant rats Anesthesia and Analgesia 2011 112 2 454 459 2-s2.0-79251630715 21081778
  130. [139]Shen C-H Tsai R-Y Tai Y-H Lin S-L Chien C-C Wong C-S Intrathecal etanercept partially restores morphines antinociception in morphine-tolerant rats via attenuation of the glutamatergic transmission Anesthesia and Analgesia 2011 113 1 184 190 2-s2.0-79960272630 21490086
  131. [140]Choi JI Svensson CI Koehrn FJ Bhuskute A Sorkin LS Peripheral inflammation induces tumor necrosis factor dependent AMPA receptor trafficking and Akt phosphorylation in spinal cord in addition to pain behavior Pain 2010 149 2 243 253 2-s2.0-77951767621 20202754 PMC2860679
  132. [141]Tobinick EL Gross H Rapid improvement in verbal fluency and aphasia following perispinal etanercept in Alzheimer’s disease BMC Neurology 2008 8 article 27 2-s2.0-49949104408 PMC2500042 18644112
  133. [142]Tobinick E Gross H Weinberger A Cohen H TNF-alpha modulation for treatment of Alzheimer’s disease: a 6-month pilot study Medscape General Medicine 2006 8 2, article 25 2-s2.0-33646201107 PMC1785182 16926764
  134. [143]van Oosten BW Barkhof F Truyen L Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2 Neurology 1996 47 6 1531 1534 8960740
  135. [144]Stommel EW Cohen JA Fadul CE Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: a phase II open label clinical trial Amyotrophic Lateral Sclerosis 2009 10 5-6 393 404 2-s2.0-70449718115 19922130 PMC3820489
  136. [145]Gowing G Dequen F Soucy G Julien J-P Absence of tumor necrosis factor-α does not affect motor neuron disease caused by superoxide dismutase 1 mutations The Journal of Neuroscience 2006 26 44 11397 11402 2-s2.0-33750962014 17079668 PMC6674545
  137. [146]Ghezzi P Mennini T Tumor necrosis factor and motoneuronal degeneration: an open problem NeuroImmunomodulation 2001 9 4 178 182 2-s2.0-0035719745 11847479
  138. [147]Bruce AJ Boling W Kindy MS Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors Nature Medicine 1996 2 7 788 794 8673925
  139. [148]Sullivan PG Bruce-Keller AJ Rabchevsky AG Exacerbation of damage and altered NF-κB activation in mice lacking tumor necrosis factor receptors after traumatic brain injury The Journal of Neuroscience 1999 19 15 6248 6256 2-s2.0-0033178340 10414954 PMC6782813
  140. [149]Jeohn G-H Kong L-Y Wilson B Hudson P Hong J-S Synergistic neurotoxic effects of combined treatments with cytokines in murine primary mixed neuron/glia cultures Journal of Neuroimmunology 1998 85 1 1 10 2-s2.0-0032077890 9626992
  141. [150]Chao CC Hu S Ehrlich L Peterson PK Interleukin-1 and tumor necrosis factor-α synergistically mediate neurotoxicity: Involvement of nitric oxide and of N-methyl-D-aspartate receptors Brain, Behavior, and Immunity 1995 9 4 355 365 2-s2.0-0029620390 8903852

Cited by

Sorted by citations

Authors
Olmos, G., & Lladó, J.
Affiliations
Research Institute of Health Sciences (ES)
Corresponding author
Olmos, Gabriel
ORCID
Venue
Mediators of Inflammation
Publisher
Wiley
Published
2014
Volume
2014
Pages
1-12
ISSN
  • 0962-9351 (ISSN-L)
  • 1466-1861
DOI
10.1155/2014/861231
PMC
PMC4055424
OpenAlex
W2033283555
Cited by
730
References
9
Citations by year
2026: 70 · 2025: 67 · 2024: 74 · 2023: 58 · 2022: 64 · 2021: 81 · 2020: 57 · 2019: 61 · 2018: 63 · 2017: 51 · 2016: 41 · 2015: 35 · 2014: 6
FWCI
3.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Mediators of Inflammation (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Docusalut (Conselleria de Salut i Consum del Govern de les Illes Balears) (submittedVersion, cc-by)
  • Hispana (submittedVersion, cc-by)
Funders
Programa Pont la Caixa per a grups de recerca de la UIB
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
TNF-α, neuroinflammation, excitotoxicity, microglial activation, glutamate uptake, astrocytes, AMPA receptors, NMDA receptor, GABAA receptor, excitation-inhibition balance, neurodegenerative diseases, amyotrophic lateral sclerosis, chronic opioid exposure, neuropathic pain, TNF signaling
MeSH terms
Analgesics, Opioid, Animals, Astrocytes, Calcium, Humans, Inflammation, Synaptic Transmission, Neuralgia, Neuroglia, Neuronal Plasticity, Neurons, Receptors, GABA-A, Tumor Necrosis Factor-alpha, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Cytokines, Receptors, Glutamate, Receptors, AMPA, Glutamic Acid

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review