Advertisement

Role of COX-2 in Inflammatory and Degenerative Brain Diseases

  • Luisa Minghetti
Part of the Subcellular Biochemistry book series (SCBI, volume 42)

In the last decade, the potential role of cyclooxygenase-2 (COX-2) and prostaglandins (PGs) in brain diseases has been extensively studied. COX-2 over-expression has been associated with neurotoxiticy in acute conditions, such as hypoxia/ischemia and seizures, as well as in inflammatory chronic diseases, including Creutzfeldt-Jakob disease (CJD) and Alzheimer’s disease (AD). However, the role played by COX-2 in neurodegenerative diseases is still controversial and further clinical and experimental studies are warranted. In addition, the emerging role of COX-2 in behavioural and cognitive functions strongly indicates that studies aimed at improving our knowledge of the physiological role of COX-2 in the central nervous system are crucial to fully understand the pros and cons of its manipulation in disabling neurological diseases

Keywords

Microglial Cell Prion Disease Bovine Spongiform Encephalopathy Kynurenic Acid Transmissible Spongiform Encephalopathy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aisen P.S., Schafer K.A., Grundman M., Pfeiffer E., Sano M., Davis K.L., Farlow M.R., Jin S., ThomasR.G., Thal L.J. Alzheimer’s Disease Cooperative Study. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 2003; 289:2819–2826.PubMedCrossRefGoogle Scholar
  2. Aisen P.S. The potential of anti-inflammatory drugs for the treatment of Alzheimer’s disease. The Lancet Neurology 2002; 1:279–284.CrossRefGoogle Scholar
  3. Baker C.A., Lu Z.Y., Zaitsev I., Manuelidis L. Microglial activation varies in different models of Creutzfeldt-Jakob disease. J Virol 1999; 73:5089–5097.PubMedGoogle Scholar
  4. Bate C., Rutherford S., Gravenor M., Reid S., Williams A. Cyclo-oxygenase inhibitors protect against prion-induced neurotoxicity in vitro. Neuroreport 2002; 13:1933–1938.PubMedCrossRefGoogle Scholar
  5. Bazan N.G. Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J Lipid Res 2003; 44:2221–2233.PubMedCrossRefGoogle Scholar
  6. Betmouni S., Perry V.H., Gordon J.L. Evidence for an early inflammatory response in the central nervous system of mice with scrapie. Neuroscience 1996; 74:1–5.PubMedCrossRefGoogle Scholar
  7. Blais V., Zhang J., Rivest S. In altering the release of glucocorticoids, ketorolac exacerbates the effects of systemic immune stimuli on expression of proinflammatory genes in the brain. Endocrinology. 2002; 143:4820–4827.PubMedCrossRefGoogle Scholar
  8. Blais V., Turrin N.P., Rivest S. Cyclooxygenase 2 (COX-2) inhibition increases the inflammatory response in the brain during systemic immune stimuli. J Neurochem 2005; 95:1563–1574.PubMedCrossRefGoogle Scholar
  9. Bosetti F., Langenbach R., Weerasinghe G.R. Prostaglandin E2 and microsomal prostaglandin E synthase-2 expression are decreased in the cyclooxygenase-2-deficient mouse brain despite compensatory induction of cyclooxygenase-1 and Ca2+-dependent phospholipase A2. J Neurochem 2004; 91:1389–1397.PubMedCrossRefGoogle Scholar
  10. Botting R.M. Mechanism of action of acetaminophen: is there a cyclooxygenase 3? Clin Infect Dis 2000; 31:S202–S210.PubMedCrossRefGoogle Scholar
  11. Breder C.D., Dewitt D., Kraig R.P. Characterization of inducible cyclooxygenase in rat brain. J Comp Neurol 1995; 355:296–315.PubMedCrossRefGoogle Scholar
  12. Candelario-Jalil E., Gonzalez-Falcon A., Garcia-Cabrera M., Alvarez D., Al-Dalain S., Martinez G., Leon O.S., Springer J.E. Assessment of the relative contribution of COX-1 and COX-2 isoforms to ischemia-induced oxidative damage and neurodegeneration following transient global cerebral ischemia. J Neurochem 2003; 86:545–555.PubMedCrossRefGoogle Scholar
  13. Chandrasekharan N.V., Dai H., Roos K.L., Evanson N.K., Tomsik J., Elton T.S., Simmons D.L. COX-3, a cycloxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure and expression. Proc. Natl Acad Sci USA 2002; 99:13926–13931.PubMedCrossRefGoogle Scholar
  14. Chang J.W., Coleman P.D., O’Banion M.K. Prostaglandin G/H synthase-2 (cyclooxygenase-2) mRNA expression is decreased in Alzheimer’s disease. Neurobiol Aging 1996; 17:801–808.PubMedCrossRefGoogle Scholar
  15. Chen C., Magee J.C., Bazan N.G. Cyclooxygenase-2 regulates prostaglandin E2 signaling in hippocampal long-term synaptic activity. J Neurophysiol 2002; 87:2851–2857.PubMedGoogle Scholar
  16. Combrinck M., Williams J., De Berardinis M.A., Warden D., Puopolo M., Smith A.D., Minghetti L. Levels of CSF prostaglandin E2, cognitive decline, and survival in Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2006; 77:85–88.PubMedCrossRefGoogle Scholar
  17. De Simone R., Ajmone-Cat M.A., Minghetti L. Atypical antiinflammatory activation of microglia induced by apoptotic neurons: possible role of phosphatidylserine-phosphatidylserine receptor interaction. Mol Neurobiol 2004; 29:197–212.PubMedCrossRefGoogle Scholar
  18. Deininger M.H., Bekure-Nemariam K., Trautmann K., Morgalla M., Meyermann R., Schluesener H.J. Cyclooxygenase-1 and -2 in brains of patients who died with sporadic Creutzfeldt-Jakob disease. J Mol Neurosci 2003; 20:25–30.PubMedCrossRefGoogle Scholar
  19. Ek M., Engblom D., Saha S., Blomqvist A., Jakobsson P., Ericsson-Dahlstrand A. Inflammatory response: pathway across the blood-brain barrier. Nature 2001; 410:430–431.PubMedCrossRefGoogle Scholar
  20. Firuzi O., Pratico D. Coxibs and Alzheimer’s disease: should they stay or should they go? Ann Neurol 2006; 59:219–228.PubMedCrossRefGoogle Scholar
  21. Forman M.S., Trojanowski J.Q., Lee V.M. Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nat Med 2004; 10:1055–1063.PubMedCrossRefGoogle Scholar
  22. Graham S.H., Hickey R.W. Cyclooxygenases in central nervous system diseases: a special role for cyclooxygenase 2 in neuronal cell death. Arch Neurol 2003; 60:628–630.PubMedCrossRefGoogle Scholar
  23. Gray F., Chretien F., Adle-Biassette H., Dorandeu A., Ereau T., Delisle M.B., Kopp N., Ironside J.W., Vital C. Neuronal apoptosis in Creutzfeldt-Jakob disease. J Neuropathol Exp Neurol 1999; 58:321–328.PubMedGoogle Scholar
  24. Guenther K., Deacon R.M., Perry V.H., Rawlins J.N. Early behavioural changes in scrapie-affected mice and the influence of dapsone. Eur J Neurosci 2001; 14:401–409.PubMedCrossRefGoogle Scholar
  25. Hinz B., Brune K. Cyclooxygenase-2– 10 years later. J Pharm Exp Ther 2002; 300:367–75.CrossRefGoogle Scholar
  26. Holscher C. Inhibitors of cyclooxygenase produce amnesia for passive avoidance task in the chick. Eur J Neurosci 1995; 7:1360–1365.PubMedCrossRefGoogle Scholar
  27. Hoozemans J.J., Bruckner M.K., Rozemuller A.J., Veerhuis R., Eikelenboom P., Arendt T. Cyclin D1 and cyclin E are co-localized with cyclo-oxygenase 2 (COX-2) in pyramidal neurons in Alzheimer disease temporal cortex. J Neuropathol Exp Neurol 2002; 61:678–688.PubMedGoogle Scholar
  28. Hoozemans J.J., Veerhuis R., Rozemuller A.J., Arendt T., Eikelenboom P. Neuronal COX-2 expression and phosphorylation of pRb precede p38 MAPK activation and neurofibrillary changes in AD temporal cortex. Neurobiol Dis 2004; 15:492–499.PubMedCrossRefGoogle Scholar
  29. Hoozemans J.J., van Haastert E.S., Veerhuis R., Arendt T., Scheper W., Eikelenboom P., Rozemuller A.J. Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer’s disease. J Neuroinflammation. 2005; 2:27.PubMedCrossRefGoogle Scholar
  30. in t’ Veld B.A., Ruitenberg A., Hofman A., Launer L.J., van Duijn C.M., Stijnen T., Breteler M.M., Stricker B.H. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med 2001; 345:1515–1521.CrossRefGoogle Scholar
  31. Kaufmann W.E., Andreasson K.I., Isakson P.C., Worley P.F. Cyclooxygenases and the central nervous system. Prostaglandins 1997; 54:601–624.PubMedCrossRefGoogle Scholar
  32. Kaufmann W.E., Worley P.F., Pegg J., Bremer M., Isakson P. COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex. Proc Natl Acad Sci U S A 1996; 93:2317–2321.PubMedCrossRefGoogle Scholar
  33. Kaufmann W.E., Worley P.F., Taylor C.V., Bremer M., Isakson P.C. Cyclooxygenase-2 expression during rat neocortical development and in Rett syndrome. Brain Dev 1997; 19:25–34PubMedCrossRefGoogle Scholar
  34. Kis B., Snipes J.A., Busija D.W. Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties. J Pharmacol Exp Ther 2005; 315:1–7.PubMedCrossRefGoogle Scholar
  35. Levi G., Minghetti L., Aloisi F. Regulation of prostanoid synthesis in microglial cells and effects of prostaglandin E2 on microglial functions. Biochimie. 1999; 80:899–904.CrossRefGoogle Scholar
  36. Lukiw W.J., Bazan N.G. Cyclooxygenase 2 RNA message abundance, stability, and hypervariability in sporadic Alzheimer neocortex. J Neurosci Res 1997; 50:937–945.PubMedCrossRefGoogle Scholar
  37. Manuelidis L., Fritch W., Zaitsev I. Dapsone to delay symptoms in Creutzfeldt-Jakob disease. Lancet 1998; 352:456.PubMedCrossRefGoogle Scholar
  38. McGeer P.L., McGeer E.G. Inflammation, autotoxicity and Alzheimer disease. Neurobiol Aging. 2001; 22:799–809.PubMedCrossRefGoogle Scholar
  39. McGeer P.L., Rogers J. Anti-inflammatory agents as a therapeutic approach to Alzheimer’s disease. Neurology. 1992; 42:447–449.PubMedGoogle Scholar
  40. Minghetti L., Cardone F., Greco A., Puopolo M., Levi G., Green A.J., Knight R., Pocchiari M. Increased CSF levels of prostaglandin E2 in variant Creutzfeldt-Jakob disease. Neurology 2002; 58:127–129.PubMedGoogle Scholar
  41. Minghetti L., Greco A., Cardone F., Puopolo M., Ladogana A., Almonti S., Cunningham C., Perry V.H., Pocchiari M., Levi G. Increased brain synthesis of prostaglandin E2 and F2-isoprostane in human and experimental transmissible spongiform encephalopathies. J Neuropathol Exp Neurol 2000; 59:866–871PubMedGoogle Scholar
  42. Minghetti L., Levi G. Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog Neurobiol 1998; 54:99–125.PubMedCrossRefGoogle Scholar
  43. Minghetti L., Sbriccoli M., Geloso M.C., Ingrosso L., Di Bari M.A., Greco A., Cardone F., Pocchiari M. Cyclooxygenases and prostaglandin E2 in animal and human prion diseases. Proceedings VII European Meeting on glial cell functions. 2005 May 17–21, Amsterdam. Medimond International Proceeding Publishers,2005.Google Scholar
  44. Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol 2004; 63:901–910.PubMedGoogle Scholar
  45. Montine T.J., Sidell K.R., Crews B.C., Markesbery W.R., Marnett L.J., Roberts L.J. 2nd, Morrow J.D. Elevated CSF prostaglandin E2 levels in patients with probable AD. Neurology 1999; 53:1495–1498.PubMedGoogle Scholar
  46. Nagy Z., Esiri M.M., Smith A.D. The cell division cycle and the pathophysiology of Alzheimer’s disease. Neuroscience 1998; 87:731–739.PubMedCrossRefGoogle Scholar
  47. Niwa K., Araki E., Morham S.G., Ross M.E., Iadecola C. Cyclooxygenase-2 contributes to functional hyperemia in whisker-barrel cortex. J Neurosci 2000; 20:763–770.PubMedGoogle Scholar
  48. O’Neill G.P., Ford-Hutchinson A.W. Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett. 1993; 330:156–160.PubMedCrossRefGoogle Scholar
  49. Parente L., Perretti M. Advances in the pathophysiology of constitutive and inducible cyclooxygenases: two enzymes in the spotlight. Biochem Pharmacol 2003; 65:153–159.PubMedCrossRefGoogle Scholar
  50. Pasinetti G.M., Aisen P.S. Cyclooxygenase-2 expression is increased in frontal cortex of Alzheimer’s disease brain. Neuroscience 1998; 87:319–324.PubMedCrossRefGoogle Scholar
  51. Pepicelli O., Fedele E., Berardi M., Raiteri M., Levi G., Greco A., Ajmone-Cat M.A., Minghetti L. Cyclo oxygenase-1 and -2 differently contribute to prostaglandin E2 synthesis and lipid peroxidation after in vivo activation of N-methyl-D-aspartate receptors in rat hippocampus. J Neurochem 2005; 93:1561–1567.PubMedCrossRefGoogle Scholar
  52. Perry V.H., Cunningham C., Boche D. Atypical inflammation in the central nervous system in prion disease. Curr Opin Neurol 2002; 15:349–354.PubMedCrossRefGoogle Scholar
  53. Puoti G., Giaccone G., Mangieri M., Limido L., Fociani P., Zerbi P., Suardi S., Rossi G., Iussich S., Capobianco R., Di Fede G., Marcon G., Cotrufo R., Filippini G., Bugiani O., Tagliavini F. Sporadic Creutzfeldt-Jakob disease: the extent of microglia activation is dependent on the biochemical type of PrPSc. J Neuropathol Exp Neurol 2005; 64:902–909.PubMedGoogle Scholar
  54. Qin N., Zhang S.P., Reitz T.L., Mei J.M., Flores C.M. Cloning, expression, and functional characterization of human cyclooxygenase-1 splicing variants: evidence for intron 1 retention. J Pharmacol Exp Ther. 2005; 315:1298–305.PubMedCrossRefGoogle Scholar
  55. Rall J.M., Mach S.A., Dash P.K. Intrahippocampal infusion of a cyclooxygenase-2 inhibitor attenuates memory acquisition in rats. Brain Res 2003; 968:273–276.PubMedCrossRefGoogle Scholar
  56. Reines S.A., Block G.A., Morris J.C., Liu G., Nessly M.L., Lines C.R., Norman B.A., Baranak C.C. Rofecoxib Protocol 091 Study Group. Rofecoxib: no effect on Alzheimer’s disease in a 1-year, randomized, blinded, controlled study. Neurology. 2004; 62:66–71.PubMedGoogle Scholar
  57. Ricceri L., Minghetti L., Moles A., Popoli P., Confaloni A., De Simone R., Piscopo P., Scattoni M.L., di Luca M., Calamandrei G. Cognitive and neurological deficits induced by early and prolonged basal forebrain cholinergic hypofunction in rats. Exp Neurol. 2004; 189:162–172.PubMedCrossRefGoogle Scholar
  58. Sang N., Zhang J., Marcheselli V., Bazan N.G., Chen C. Postsynaptically synthesized prostaglandin E2 (PGE2) modulates hippocampal synaptic transmission via a presynaptic PGE2 EP2 receptor. J Neurosci. 2005; 25:9858–9870.PubMedCrossRefGoogle Scholar
  59. Sharifzadeh M., Naghdi N., Khosrovani S., Ostad S.N., Sharifzadeh K., Roghani A. Post-training intrahippocampal infusion of the COX-2 inhibitor celecoxib impaired spatial memory retention in rats. Eur J Pharmacol. 2005; 511:159–166.PubMedCrossRefGoogle Scholar
  60. Sharifzadeh M., Tavasoli M., Soodi M., Mohammadi-Eraghi S., Ghahremani M.H., Roghani A. A time course analysis of cyclooxygenase-2 suggests a role in spatial memory retrieval in rats. Neurosci Res. 2006; 54:171–179.PubMedCrossRefGoogle Scholar
  61. Schwab J.M., Schluesener H.J. Cyclooxygenases and central nervous system inflammation: conceptual neglect of cyclooxygenase 1. Arch Neurol 2003; 60:630–632.PubMedCrossRefGoogle Scholar
  62. Schwieler L., Erhardt S., Nilsson L., Linderholm K., Engberg G. Effects of COX-1 and COX-2 inhibitors on the firing of rat midbrain dopaminergic neurons–possible involvement of endogenous kynurenic acid. Synapse. 2006; 59:290–298.PubMedCrossRefGoogle Scholar
  63. Shaftel S.S., Olschowka J.A., Hurley S.D., Moore A.H., O’Banion M.K. COX-3: a splice variant of cyclooxygenase-1 in mouse neural tissue and cells. Brain Res Mol Brain Res 2003; 119:213–215.PubMedCrossRefGoogle Scholar
  64. Shaw K.N., Commins S., O’Mara S.M. Deficits in spatial learning and synaptic plasticity induced by the rapid and competitive broad-spectrum cyclooxygenase inhibitor ibuprofen are reversed by increasing endogenous brain-derived neurotrophic factor. Eur J Neurosci 2003; 17:2438–46.PubMedCrossRefGoogle Scholar
  65. Simard A.R., Rivest S. Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer’s disease. Mol Psychiatry 2006; 11:327–335.PubMedCrossRefGoogle Scholar
  66. Sternberg E.M. Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens. Nat Rev Immunol. 2006; 6:318–328.PubMedCrossRefGoogle Scholar
  67. Streit W.J. Microglia as neuroprotective, immunocompetent cells of the CNS. Glia. 2002; 40:133–139.PubMedCrossRefGoogle Scholar
  68. Teather L.A., Packard M.G., Bazan N.G. Post-training cyclooxygenase-2 (COX-2) inhibition impairs memory consolidation. Learn Mem 2002; 9:41–47.PubMedCrossRefGoogle Scholar
  69. Vazquez-Tello A., Fan L., Hou X., Joyal J.S., Mancini J.A., Quiniou C., Clyman R.I., Gobeil F.Jr, Varma D.R., Chemtob S. Intracellular-specific colocalization of prostaglandin E2 synthases and cyclooxygenases in the brain. Am J Physiol Regul Integr Comp Physiol. 2004; 287:R1155–R1163.PubMedGoogle Scholar
  70. Walsh D.T., Perry V.H., Minghetti L. Cyclooxygenase-2 is highly expressed in microglial-like cells in a murine model of prion disease. Glia 2000; 29:392–396PubMedCrossRefGoogle Scholar
  71. Webber K.M., Raina A.K., Marlatt M.W., Zhu X., Prat M.I., Morelli L., Casadesus G., Perry G., Smith M.A. The cell cycle in Alzheimer disease: a unique target for neuropharmacology. Mech Ageing Dev. 2005; 126:1019–1025.PubMedCrossRefGoogle Scholar
  72. Will R.G., Alperovitch A., Poser S., Pocchiari M., Hofman A., Mitrova E., de Silva R., D’Alessandro M. Delasnerie-Laupretre N., Zerr I., van Duijn C. Descriptive epidemiology of Creutzfeldt-Jakob disease in six European countries, 1993–1995. EU Collaborative Study Group for CJD. Ann Neurol. 1998; 43:763–767.PubMedCrossRefGoogle Scholar
  73. Will R.G., Ironside J.W., Zeidler M., Cousens S.N., Estibeiro K., Alperovitch A., Poser S., Pocchiari M, Hofman A., Smith P.G. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996; 347:921–925PubMedCrossRefGoogle Scholar
  74. Yamagata K., Andreasson K.I., Kaufmann W.E., Barnes C.A., Worley P.F. Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron 1993; 11:371–386.PubMedCrossRefGoogle Scholar
  75. Yasojima K., Schwab C., McGeer E.G., McGeer P.L. Distribution of cyclooxygenase-1 and cyclooxygenase-2 mRNAs and proteins in human brain and peripheral organs. Brain Res 1999; 830:226–236.PubMedCrossRefGoogle Scholar
  76. Yermakova A.V., O’Banion M.K. Downregulation of neuronal cyclooxygenase-2 expression in end stage Alzheimer’s disease. Neurobiol Aging 2001; 22:823–836.PubMedCrossRefGoogle Scholar
  77. Yermakova A.V., Rollins J., Callahan L.M., Rogers J., O’Banion M.K. Cyclooxygenase-1 in human Alzheimer’s, and control brain: quantitative analysis of expression by microglia and CA3 hippocampal neurons. J Neuropathol Exp Neurol 1999; 58:1135–1146.PubMedCrossRefGoogle Scholar
  78. Zhang J., Rivest S. Anti-inflammatory effects of prostaglandin E2 in the central nervous system in response to brain injury and circulating lipopolysaccharide. J Neurochem 2001; 76:855–64.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Luisa Minghetti
    • 1
  1. 1.Department of Cell Biology and NeurosciencesIstituto Superiore di SanitáRomeItaly

Personalised recommendations