Advertisement

Apoptosis

, Volume 15, Issue 11, pp 1382–1402 | Cite as

Molecular and cellular mechanisms of excitotoxic neuronal death

  • Yan Wang
  • Zheng-hong QinEmail author
Apoptosis in the aging brain

Abstract

Glutamate receptor-mediated excitatory neurotransmission plays a key role in neural development, differentiation and synaptic plasticity. However, excessive stimulation of glutamate receptors induces neurotoxicity, a process that has been defined as excitotoxicity. Excitotoxicity is considered to be a major mechanism of cell death in a number of central nervous system diseases including stroke, brain trauma, epilepsy and chronic neurodegenerative disorders. Unfortunately clinical trials with glutamate receptor antagonists, that would logically prevent the effects of excessive receptor activation, have been associated with untoward side effects or little clinical benefit. Therefore, uncovering molecular pathways involved in excitotoxic neuronal death is of critical importance to future development of clinical treatment of many neurodegenerative disorders where excitotoxicity has been implicated. This review discusses the current understanding of the molecular and cellular mechanisms of excitotoxicity and their roles in the pathogenesis of diseases of the central nervous system.

Keywords

Excitotoxicity Glutamate receptor Mitochondria Protease Neurological disorder 

Notes

Acknowledgment

This work was supported by grants from The Natural Science Foundation of China (No. 30772560; No. 30930035).

References

  1. 1.
    Suzuki M, Nelson AD, Eickstaedt JB, Wallace K, Wright LS, Svendsen CN (2006) Glutamate enhances proliferation and neurogenesis in human neural progenitor cell cultures derived from the fetal cortex. Eur J Neurosci 24:645–653PubMedCrossRefGoogle Scholar
  2. 2.
    Olney JW (1969) Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 164:719–721PubMedCrossRefGoogle Scholar
  3. 3.
    Bruijn LI, Miller TM, Cleveland DW (2004) Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 27:723–749PubMedCrossRefGoogle Scholar
  4. 4.
    Doble A (1999) The role of excitotoxicity in neurodegenerative disease: implications for therapy. Pharmacol Ther 81:163–221PubMedCrossRefGoogle Scholar
  5. 5.
    Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–108PubMedCrossRefGoogle Scholar
  6. 6.
    Pin JP, Duvoisin R (1995) The metabotropic glutamate receptors: structure and functions. Neuropharmacology 34:1–26PubMedCrossRefGoogle Scholar
  7. 7.
    Arundine M, Tymianski M (2004) Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury. Cell Mol Life Sci 61:657–668PubMedCrossRefGoogle Scholar
  8. 8.
    Cristofanilli M, Akopian A (2006) Calcium channel and glutamate receptor activities regulate actin organization in salamander retinal neurons. J Physiol 575:543–554PubMedCrossRefGoogle Scholar
  9. 9.
    Liot G, Bossy B, Lubitz S, Kushnareva Y, Sejbuk N, Bossy-Wetzel E (2009) Complex II inhibition by 3-NP causes mitochondrial fragmentation and neuronal cell death via an NMDA- and ROS-dependent pathway. Cell Death Differ 16:899–909PubMedCrossRefGoogle Scholar
  10. 10.
    Rego AC, Oliveira CR (2003) Mitochondrial dysfunction and reactive oxygen species in excitotoxicity and apoptosis: implications for the pathogenesis of neurodegenerative diseases. Neurochem Res 28:1563–1574PubMedCrossRefGoogle Scholar
  11. 11.
    Ward MW, Rego AC, Frenguelli BG, Nicholls DG (2000) Mitochondrial membrane potential and glutamate excitotoxicity in cultured cerebellar granule cells. J Neurosci 20:7208–7219PubMedGoogle Scholar
  12. 12.
    Burnashev N, Monyer H, Seeburg PH, Sakmann B (1992) Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron 8:189–198PubMedCrossRefGoogle Scholar
  13. 13.
    Köhr G, Melcher T, Seeburg PH (1998) Candidate editases for GluR channels in single neurons of rat hippocampus and cerebellum. Neuropharmacology 37:1411–1417PubMedCrossRefGoogle Scholar
  14. 14.
    Carriedo SG, Yin HZ, Weiss JH (1996) Motor neurons are selectively vulnerable to AMPA/kainate receptor-mediated injury in vitro. J Neurosci 16:4069–4079PubMedGoogle Scholar
  15. 15.
    Friedman LK, Ginsberg MD, Belayev L, Busto R, Alonso OF, Lin B, Globus MY-T (2001) Intraischemic but not postischemic hypothermia prevents non-selective hippocampal downregulation of AMPA and NMDA receptor gene expression after global ischemia. Mol Brain Res 86:34–47PubMedCrossRefGoogle Scholar
  16. 16.
    Gottlieb M, Matute C (1997) Expression of ionotropic glutamate receptor subunits in glial cells of the hippocampal CA1 area following transient forebrain ischemia. J Cereb Blood Flow Metab 17:290–300PubMedCrossRefGoogle Scholar
  17. 17.
    Friedman LK (2006) Calcium: a role for neuroprotection and sustained adaptation. Mol Interv 6:315–329PubMedCrossRefGoogle Scholar
  18. 18.
    Friedman LK, Avallone JM, Magrys B (2007) Maturational effects of single and multiple early-life seizures on AMPA receptors in prepubescent hippocampus. Dev Neurosci 29:427–437PubMedCrossRefGoogle Scholar
  19. 19.
    Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61PubMedGoogle Scholar
  20. 20.
    Berman FW, Murray TF (1997) Domoic acid neurotoxicity in cultured cerebellar granule neurons is mediated predominantly by NMDA receptors that are activated as a consequence of excitatory amino acid release. J Neurochem 69:693–703PubMedCrossRefGoogle Scholar
  21. 21.
    Ferkany JW, Zaczek R, Coyle JT (1982) Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors. Nature 298:757–759PubMedCrossRefGoogle Scholar
  22. 22.
    Wang Y, Gu ZL, Cao Y, Liang ZQ, Han R, Bennett MC, Qin ZH (2006) Lysosomal enzyme cathepsin B is involved in kainic acid-induced excitotoxicity in rat striatum. Brain Res 1071:245–249PubMedCrossRefGoogle Scholar
  23. 23.
    Wang Y, Han R, Liang ZQ, Wu JC, Zhang XD, Gu ZL, Qin ZH (2008) An autophagic mechanism is involved in apoptotic death of rat striatal neurons induced by the non-N-methyl-D-aspartate receptor agonist kainic acid. Autophagy 4:214–226PubMedGoogle Scholar
  24. 24.
    Pin JP, Acher F (2002) The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. Curr Drug Targets CNS Neurol Disord 1:297–317PubMedCrossRefGoogle Scholar
  25. 25.
    Collin T, Franconville R, Ehrlich BE, Llano I (2009) Activation of metabotropic glutamate receptors induces periodic burst firing and concomitant cytosolic Ca2+ oscillations in cerebellar interneurons. J Neurosci 29:9281–9291PubMedCrossRefGoogle Scholar
  26. 26.
    Lan JY, Skeberdis VA, Jover T, Zheng X, Bennett MV, Zukin RS (2001) Activation of metabotropic glutamate receptor 1 accelerates NMDA receptor trafficking. J Neurosci 21:6058–6068PubMedGoogle Scholar
  27. 27.
    Anwyl R (1999) Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Res Rev 29:83–120PubMedCrossRefGoogle Scholar
  28. 28.
    Faden AI, O’Leary DM, Fan L, Bao W, Mullins PG, Movsesyan VA (2001) Selective blockade of the mGluR1 receptor reduces traumatic neuronal injury in vitro and improvesoOutcome after brain trauma. Exp Neurol 167:435–444PubMedCrossRefGoogle Scholar
  29. 29.
    Mukhin A, Fan L, Faden AI (1996) Activation of metabotropic glutamate receptor subtype mGluR1 contributes to post-traumatic neuronal injury. J Neurosci 16:6012–6020PubMedGoogle Scholar
  30. 30.
    Wang Y, Qin ZH, Nakai M, Chase TN (1997) Glutamate metabotropic receptor agonist 1S, 3R-ACPD induces internucleosomal DNA fragmentation and cell death in rat striatum. Brain Res 772:45–56PubMedCrossRefGoogle Scholar
  31. 31.
    Bruno V, Battaglia G, Copani A, Giffard RG, Raciti G, Raffaele R, Shinozaki H, Nicoletti F (1995) Activation of class II or III metabotropic glutamate receptors protects cultured cortical neurons against excitotoxic degeneration. Eur J Neurosci 7:1906–1913PubMedCrossRefGoogle Scholar
  32. 32.
    Di Iorio P, Battaglia G, Ciccarelli R, Ballerini P, Giuliani P, Poli A, Nicoletti F, Caciagli F (1996) Interaction between A1 adenosine and class II metabotropic glutamate receptors in the regulation of purine and glutamate release from rat hippocampal slices. J Neurochem 67:302–309PubMedCrossRefGoogle Scholar
  33. 33.
    Buisson A, Choi DW (1995) The inhibitory mGluR agonist, S-4-carboxy-3-hydroxy-phenylglycine selectively attenuates NMDA neurotoxicity and oxygen-glucose deprivation-induced neuronal death. Neuropharmacology 34:1081–1087PubMedCrossRefGoogle Scholar
  34. 34.
    Iacovelli L, Bruno V, Salvatore L, Melchiorri D, Gradini R, Caricasole A, Barletta E, De Blasi A, Nicoletti F (2002) Native group-III metabotropic glutamate receptors are coupled to the mitogen-activated protein kinase/phosphatidylinositol-3-kinase pathways. J Neurochem 82:216–223PubMedCrossRefGoogle Scholar
  35. 35.
    Mills CD, Xu GY, McAdoo DJ, Hulsebosch CE (2001) Involvement of metabotropic glutamate receptors in excitatory amino acid and GABA release following spinal cord injury in rat. J Neurochem 79:835–848PubMedCrossRefGoogle Scholar
  36. 36.
    Golstein P, Kroemer G (2007) Cell death by necrosis: towards a molecular definition. Trends Biochem Sci 32:37–43PubMedCrossRefGoogle Scholar
  37. 37.
    Pohl D, Bittigau P, Ishimaru MJ, Stadthaus D, Hübner C, Olney JW, Turski L, Ikonomidou C (1999) N-Methyl-D-aspartate antagonists and apoptotic cell death triggered by head trauma in developing rat brain. Proc Natl Acad Sci USA 96:2508–2513PubMedCrossRefGoogle Scholar
  38. 38.
    Qin ZH, Wang Y, Chase TN (1996) Stimulation of N-methyl-D-aspartate receptors induces apoptosis in rat brain. Brain Res 725:166–176PubMedGoogle Scholar
  39. 39.
    Martin LJ, Al-Abdulla NA, Brambrink AM, Kirsch JR, Sieber FE, Portera-Cailliau C (1998) Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: a perspective on the contributions of apoptosis and necrosis. Brain Res Bull 46:281–309PubMedCrossRefGoogle Scholar
  40. 40.
    Dong XX, Wang Y, Qin ZH (2009) Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases. Acta Pharmacol Sin 30:379–387PubMedCrossRefGoogle Scholar
  41. 41.
    Qin ZH, Tao LY, Chen X (2007) Dual roles of NF-kappaB in cell survival and implications of NF-kappaB inhibitors in neuroprotective therapy. Acta Pharmacol Sin 28:1859–1872PubMedCrossRefGoogle Scholar
  42. 42.
    Zhang XD, Wang Y, Wang Y, Zhang X, Han R, Wu JC, Liang ZQ, Gu ZL, Han F, Fukunaga K, Qin ZH (2009) p53 mediates mitochondria dysfunction-triggered autophagy activation and cell death in rat striatum. Autophagy 5:339–350PubMedCrossRefGoogle Scholar
  43. 43.
    Borsello T, Croquelois K, Hornung JP, Clarke PG (2003) N-methyl-D-aspartate-triggered neuronal death in organotypic hippocampal cultures is endocytic, autophagic and mediated by the c-Jun N-terminal kinase pathway. Eur J Neurosci 18:473–485PubMedCrossRefGoogle Scholar
  44. 44.
    Shacka JJ, Lu J, Xie ZL, Uchiyama Y, Roth KA, Zhang J (2007) Kainic acid induces early and transient autophagic stress in mouse hippocampus. Neurosci Lett 414:57–60PubMedCrossRefGoogle Scholar
  45. 45.
    Wang Y, Dong XX, Cao Y, Liang ZH, Han R, Wu JC, Gu ZL, Qin ZH (2009) p53 induction contributes to excitotoxic neuronal death in rat striatum through apoptotic and autophagic mechanisms. Eur J Neurosci 30:2258–2270PubMedCrossRefGoogle Scholar
  46. 46.
    Rothman SM, Olney JW (1995) Excitotoxicity and the NMDA receptor-still lethal after eight years. Trends Neurosci 18:57–58PubMedCrossRefGoogle Scholar
  47. 47.
    Aarts M, Iihara K, Wei WL, Xiong ZG, Arundine M, Cerwinski W, MacDonald JF, Tymianski M (2003) A key role for TRPM7 channels in anoxic neuronal death. Cell 115:863–877PubMedCrossRefGoogle Scholar
  48. 48.
    Xiong ZG, Zhu XM, Chu XP, Minami M, Hey J, Wei WL, MacDonald JF, Wemmie JA, Price MP, Welsh MJ, Simon RP (2004) Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell 118:687–698PubMedCrossRefGoogle Scholar
  49. 49.
    Carafoli E, Santella L, Branca D, Brini M (2001) Generation, control, and processing of cellular calcium signals. Crit Rev Biochem Mol Biol 36:107–260PubMedCrossRefGoogle Scholar
  50. 50.
    Philipson KD, Nicoll DA (2000) Sodium-calcium exchange: a molecular perspective. Annu Rev Physiol 62:111–133PubMedCrossRefGoogle Scholar
  51. 51.
    Nicoll DA, Quednau BD, Qui Z, Xia YR, Lusis AJ, Philipson KD (1996) Cloning of a third mammalian Na+-Ca2+ exchanger, NCX3. J Biol Chem 271:24914–24921PubMedCrossRefGoogle Scholar
  52. 52.
    Inglefield JR, Schwartz-Bloom RD (1998) Activation of excitatory amino acid receptors in the rat hippocampal slice increases intracellular Cl and cell volume. J Neurochem 71:1396–1404PubMedCrossRefGoogle Scholar
  53. 53.
    Rothman SM (1985) The neurotoxicity of excitatory amino acids is produced by passive chloride influx. J Neurosci 5:1483–1489PubMedGoogle Scholar
  54. 54.
    Nicklas WJ, Zeevalk G, Hyndman A (1987) Interactions between neurons and glia in glutamate/glutamine compartmentation. Biochem Soc Trans 15:208–210PubMedGoogle Scholar
  55. 55.
    Babot Z, Cristòfol R, Suñol C (2005) Excitotoxic death induced by released glutamate in depolarized primary cultures of mouse cerebellar granule cells is dependent on GABAA receptors and niflumic acid-sensitive chloride channels. Eur J Neurosci 21:103–112PubMedCrossRefGoogle Scholar
  56. 56.
    Van Damme P, Callewaert G, Eggermont J, Robberecht W, Van Den Bosch L (2003) Chloride influx aggravates Ca2+-dependent AMPA receptor-mediated motoneuron death. J Neurosci 23:4942–4950PubMedGoogle Scholar
  57. 57.
    Inoue H, Okada Y (2007) Roles of volume-sensitive chloride channel in excitotoxic neuronal injury. J Neurosci 27:1445–1455PubMedCrossRefGoogle Scholar
  58. 58.
    Russell JM (2000) Sodium-potassium-chloride cotransport. Physiol Rev 80:211–276PubMedGoogle Scholar
  59. 59.
    Alvarez-Leefmans FJ (2001) Intracellular chloride regulation. In: Sperelakis N (ed) Cell physiology sourcebook: a molecular approach, 3rd edn. Academic Press, San Diego, pp 301–318Google Scholar
  60. 60.
    Wang H, Yan Y, Kintner DB, Lytle C, Sun D (2003) GABA-mediated trophic effect on oligodendrocytes requires Na-K-2Cl cotransport activity. J Neurophysiol 90:1257–1265PubMedCrossRefGoogle Scholar
  61. 61.
    Park E, Velumian AA, Fehlings MG (2004) The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration. J Neurotrauma 21:754–774PubMedCrossRefGoogle Scholar
  62. 62.
    Micu I, Jiang Q, Coderre E, Ridsdale A, Zhang L, Woulfe J, Yin X, Trapp BD, McRory JE, Rehak R, Zamponi GW, Wang W, Stys PK (2006) NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia. Nature 439:988–992PubMedGoogle Scholar
  63. 63.
    Salter MG, Fern R (2005) NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury. Nature 438:1167–1171PubMedCrossRefGoogle Scholar
  64. 64.
    Follett PL, Rosenberg PA, Volpe JJ, Jensen FE (2000) NBQX attenuates excitotoxic injury in developing white matter. J Neurosci 20:9235–9241PubMedGoogle Scholar
  65. 65.
    Kanellopoulos GK, Xu XM, Hsu CY, Lu X, Sundt TM, Kouchoukos NT (2000) White matter injury in spinal cord ischemia: protection by AMPA/kainate glutamate receptor antagonism. Stroke 31:1945–1952PubMedGoogle Scholar
  66. 66.
    Tekkök SB, Goldberg MP (2001) Ampa/kainate receptor activation mediates hypoxic oligodendrocyte death and axonal injury in cerebral white matter. J Neurosci 21:4237–4248PubMedGoogle Scholar
  67. 67.
    Deng W, Poretz RD (2003) Oligodendroglia in developmental neurotoxicity. Neurotoxicology 24:161–178PubMedCrossRefGoogle Scholar
  68. 68.
    Fern R, Möller T (2000) Rapid ischemic cell death in immature oligodendrocytes: a fatal glutamate release feedback loop. J Neurosci 20:34–42PubMedGoogle Scholar
  69. 69.
    Ness JK, Scaduto RC Jr, Wood TL (2004) IGF-I prevents glutamate-mediated bax translocation and cytochrome C release in O4+ oligodendrocyte progenitors. Glia 46:183–194PubMedCrossRefGoogle Scholar
  70. 70.
    Yuan J, Lipinski M, Degterev A (2003) Diversity in the mechanisms of neuronal cell death. Neuron 40:401–413PubMedCrossRefGoogle Scholar
  71. 71.
    Lindholm D, Wootz H, Korhonen L (2006) ER stress and neurodegenerative diseases. Cell Death Differ 13:385–392PubMedCrossRefGoogle Scholar
  72. 72.
    Wu J, Kaufman RJ (2006) From acute ER stress to physiological roles of the Unfolded Protein Response. Cell Death Differ 13:374–384PubMedCrossRefGoogle Scholar
  73. 73.
    Nicholls DG, Ward MW (2000) Mitochondrial membrane potential and neuronal glutamate excitotoxicity: mortality and millivolts. Trends Neurosci 23:166–174PubMedCrossRefGoogle Scholar
  74. 74.
    Ankarcrona M, Dypbukt JM, Bonfoco E, Zhivotovsky B, Orrenius S, Lipton SA, Nicotera P (1995) Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron 15:961–973PubMedCrossRefGoogle Scholar
  75. 75.
    Atlante A, Calissano P, Bobba A, Giannattasio S, Marra E, Passarella S (2001) Glutamate neurotoxicity, oxidative stress and mitochondria. FEBS Lett 497:1–5PubMedCrossRefGoogle Scholar
  76. 76.
    Peng TI, Greenamyre JT (1998) Privileged access to mitochondria of calcium influx through N-methyl-D-aspartate receptors. Mol Pharmacol 53:974–980PubMedGoogle Scholar
  77. 77.
    Fiskum G (2000) Mitochondrial participation in ischemic and traumatic neural cell death. J Neurotrauma 17:843–855PubMedCrossRefGoogle Scholar
  78. 78.
    Fiskum G, Starkov A, Polster BM, Chinopoulos C (2003) Mitochondrial mechanisms of neural cell death and neuroprotective interventions in Parkinson’s disease. Ann N Y Acad Sci 991:111–119PubMedCrossRefGoogle Scholar
  79. 79.
    Rego AC, Santos MS, Oliveira CR (2000) Glutamate-mediated inhibition of oxidative phosphorylation in cultured retinal cells. Neurochem Int 36:159–166PubMedCrossRefGoogle Scholar
  80. 80.
    Castilho RF, Hansson O, Ward MW, Budd SL, Nicholls DG (1998) Mitochondrial control of acute glutamate excitotoxicity in cultured cerebellar granule cells. J Neurosci 18:10277–10286PubMedGoogle Scholar
  81. 81.
    Brown GC, Borutaite V (2008) Regulation of apoptosis by the redox state of cytochrome c. Biochim Biophys Acta 1777:877–881PubMedCrossRefGoogle Scholar
  82. 82.
    Gogvadze V, Orrenius S, Zhivotovsky B (2006) Multiple pathways of cytochrome c release from mitochondria in apoptosis. Biochim Biophys Acta 1757:639–647PubMedCrossRefGoogle Scholar
  83. 83.
    Delivoria-Papadopoulos M, Gorn M, Ashraf QM, Mishra OP (2007) ATP and cytochrome c-dependent activation of caspase-9 during hypoxia in the cerebral cortex of newborn piglets. Neurosci Lett 429:115–119PubMedCrossRefGoogle Scholar
  84. 84.
    Molz S, Decker H, Dal-Cim T, Cremonez C, Cordova FM, Leal RB, Tasca CI (2008) Glutamate-induced toxicity in hippocampal slices involves apoptotic features and p38 MAPK signaling. Neurochem Res 33:27–36PubMedCrossRefGoogle Scholar
  85. 85.
    Atlante A, Calissano P, Bobba A, Azzariti A, Marra E, Passarella S (2000) Cytochrome c is released from mitochondria in a reactive oxygen species (ROS)-dependent fashion and can operate as a ROS scavenger and as a respiratory substrate in cerebellar neurons undergoing excitotoxic death. J Biol Chem 275:37159–37166PubMedCrossRefGoogle Scholar
  86. 86.
    Luetjens CM, Bui NT, Sengpiel B, Münstermann G, Poppe M, Krohn AJ, Bauerbach E, Krieglstein J, Prehn JH (2000) Delayed mitochondrial dysfunction in excitotoxic neuron death: cytochrome c release and a secondary increase in superoxide production. J Neurosci 20:5715–5723PubMedGoogle Scholar
  87. 87.
    Tenneti L, Lipton SA (2000) Involvement of activated caspase-3-like proteases in N-methyl-D-aspartate-induced apoptosis in cerebrocortical neurons. J Neurochem 74:134–142PubMedCrossRefGoogle Scholar
  88. 88.
    Yu SW, Wang H, Poitras MF, Coombs C, Bowers WJ, Federoff HJ, Poirier GG, Dawson TM, Dawson VL (2002) Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297:259–263PubMedCrossRefGoogle Scholar
  89. 89.
    Brunk UT, Terman A (2002) The mitochondrial-lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur J Biochem 269:1996–2002PubMedCrossRefGoogle Scholar
  90. 90.
    Boyce M, Yuan J (2006) Cellular response to endoplasmic reticulum stress: a matter of life or death. Cell Death Differ 13:363–373PubMedCrossRefGoogle Scholar
  91. 91.
    Verkhratsky A (2005) Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons. Physiol Rev 85:201–279PubMedCrossRefGoogle Scholar
  92. 92.
    Bánhegyi G, Mandl J, Csala M (2008) Redox-based endoplasmic reticulum dysfunction in neurological diseases. J Neurochem 107:20–34PubMedCrossRefGoogle Scholar
  93. 93.
    Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D (2000) Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol 2:326–332PubMedCrossRefGoogle Scholar
  94. 94.
    Liu CY, Xu Z, Kaufman RJ (2003) Structure and intermolecular interactions of the luminal dimerization domain of human IRE1alpha. J Biol Chem 278:17680–17687PubMedCrossRefGoogle Scholar
  95. 95.
    Ma K, Vattem KM, Wek RC (2002) Dimerization and release of molecular chaperone inhibition facilitate activation of eukaryotic initiation factor-2 kinase in response to endoplasmic reticulum stress. J Biol Chem 277:18728–18735PubMedCrossRefGoogle Scholar
  96. 96.
    Breckenridge DG, Germain M, Mathai JP, Nguyen M, Shore GC (2003) Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 22:8608–8618PubMedCrossRefGoogle Scholar
  97. 97.
    Hetz C, Bernasconi P, Fisher J, Lee AH, Bassik MC, Antonsson B, Brandt GS, Iwakoshi NN, Schinzel A, Glimcher LH, Korsmeyer SJ (2006) Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha. Science 312:572–576PubMedCrossRefGoogle Scholar
  98. 98.
    Rao RV, Ellerby HM, Bredesen DE (2004) Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ 11:372–380PubMedCrossRefGoogle Scholar
  99. 99.
    Oyadomari S, Araki E, Mori M (2002) Endoplasmic reticulum stress-mediated apoptosis in pancreatic beta-cells. Apoptosis 7:335–345PubMedCrossRefGoogle Scholar
  100. 100.
    Uehara T, Nakamura T, Yao D, Shi ZQ, Gu Z, Ma Y, Masliah E, Nomura Y, Lipton SA (2006) S-Nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration. Nature 441:513–517PubMedCrossRefGoogle Scholar
  101. 101.
    Lerma J (2003) Roles and rules of kainate receptors in synaptic transmission. Nat Rev Neurosci 4:481–495PubMedCrossRefGoogle Scholar
  102. 102.
    Korhonen L, Hansson I, Kukkonen JP, Brännvall K, Kobayashi M, Takamatsu K, Lindholm D (2005) Hippocalcin protects against caspase-12-induced and age-dependent neuronal degeneration. Mol Cell Neurosci 28:85–95PubMedCrossRefGoogle Scholar
  103. 103.
    Shimazawa M, Inokuchi Y, Ito Y, Murata H, Aihara M, Miura M, Araie M, Hara H (2007) Involvement of ER stress in retinal cell death. Mol Vis 13:578–587PubMedGoogle Scholar
  104. 104.
    Yu Z, Luo H, Fu W, Mattson MP (1999) The endoplasmic reticulum stress-responsive protein GRP78 protects neurons against excitotoxicity and apoptosis: suppression of oxidative stress and stabilization of calcium homeostasis. Exp Neurol 155:302–314PubMedCrossRefGoogle Scholar
  105. 105.
    Sokka AL, Putkonen N, Mudo G, Pryazhnikov E, Reijonen S, Khiroug L, Belluardo N, Lindholm D, Korhonen L (2007) Endoplasmic reticulum stress inhibition protects against excitotoxic neuronal injury in the rat brain. J Neurosci 27:901–908PubMedCrossRefGoogle Scholar
  106. 106.
    Brunk UT, Neuzil J, Eaton JW (2001) Lysosomal involvement in apoptosis. Redox Rep 6:91–97PubMedCrossRefGoogle Scholar
  107. 107.
    Turk B, Stoka V, Rozman-Pungercar J, Cirman T, Droga-Mazovec G, Oresić K, Turk V (2002) Apoptotic pathways: involvement of lysosomal proteases. Biol Chem 383:1035–1044PubMedCrossRefGoogle Scholar
  108. 108.
    Tominaga K, Nakanishi H, Yasuda Y, Yamamoto K (1998) Excitotoxin-induced neuronal death is associated with response of a unique intracellular aspartic proteinase, cathepsin E. J Neurochem 71:2574–2584PubMedCrossRefGoogle Scholar
  109. 109.
    Pan T, Kondo S, Le W, Jankovic J (2008) The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson’s disease. Brain 131:1969–1978PubMedCrossRefGoogle Scholar
  110. 110.
    Rajawat YS, Hilioti Z, Bossis I (2009) Aging: central role for autophagy and the lysosomal degradative system. Ageing Res Rev 8:199–213PubMedCrossRefGoogle Scholar
  111. 111.
    Turk B, Turk V (2009) Lysosomes as “suicide bags” in cell death: myth or reality? J Biol Chem 284:21783–21787PubMedCrossRefGoogle Scholar
  112. 112.
    D’Herde K, Diez-Fraile A, Lammens T (2009) Apoptotic, autophagic and necrotic cell death types in pathophysiological conditions: morphological and histological aspects. In: Krysko DV, Vandenabeele P (eds) Phagocytosis of dying cells: from molecular mechanisms to human diseases. Springer, Netherlands, pp 33–62CrossRefGoogle Scholar
  113. 113.
    González-Polo RA, Boya P, Pauleau AL, Jalil A, Larochette N, Souquère S, Eskelinen EL, Pierron G, Saftig P, Kroemer G (2005) The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J Cell Sci 118:3091–3102PubMedCrossRefGoogle Scholar
  114. 114.
    Hsieh YC, Athar M, Chaudry IH (2009) When apoptosis meets autophagy: deciding cell fate after trauma and sepsis. Trends Mol Med 15:129–138PubMedCrossRefGoogle Scholar
  115. 115.
    Canu N, Tufi R, Serafino AL, Amadoro G, Ciotti MT, Calissano P (2005) Role of the autophagic-lysosomal system on low potassium-induced apoptosis in cultured cerebellar granule cells. J Neurochem 92:1228–1242PubMedCrossRefGoogle Scholar
  116. 116.
    Terman A, Gustafsson B, Brunk UT (2006) The lysosomal-mitochondrial axis theory of postmitotic aging and cell death. Chem Biol Interact 163:29–37PubMedCrossRefGoogle Scholar
  117. 117.
    Nixon RA, Cataldo AM, Mathews PM (2000) The endosomal-lysosomal system of neurons in Alzheimer’s disease pathogenesis: a review. Neurochem Res 25:1161–1172PubMedCrossRefGoogle Scholar
  118. 118.
    Zhang L, Sheng R, Qin Z (2009) The lysosome and neurodegenerative diseases. Acta Biochim Biophys Sin (Shanghai) 41:437–445CrossRefGoogle Scholar
  119. 119.
    Bendiske J, Bahr BA (2003) Lysosomal activation is a compensatory response against protein accumulation and associated synaptopathogenesis—an approach for slowing Alzheimer disease? J Neuropathol Exp Neurol 62:451–463PubMedGoogle Scholar
  120. 120.
    Yamashima T (2000) Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates. Prog Neurobiol 62:273–295PubMedCrossRefGoogle Scholar
  121. 121.
    Aarts MM, Arundine M, Tymianski M (2003) Novel concepts in excitotoxic neurodegeneration after stroke. Expert Rev Mol Med 5:1–22PubMedCrossRefGoogle Scholar
  122. 122.
    Farooqui AA, Ong WY, Horrocks LA (2008) Glutamate receptors and their association with other neurochemical parameters in excitotoxicity. In: Farooqui AA (ed) Neurochemical aspects of excitotoxicity, 1st edn. Springer, New York, pp 105–136Google Scholar
  123. 123.
    Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262:689–695PubMedCrossRefGoogle Scholar
  124. 124.
    Nicholls DG (2004) Mitochondrial dysfunction and glutamate excitotoxicity studied in primary neuronal cultures. Curr Mol Med 4:149–177PubMedCrossRefGoogle Scholar
  125. 125.
    Sullivan PG, Rabchevsky AG, Waldmeier PC, Springer JE (2005) Mitochondrial permeability transition in CNS trauma: cause or effect of neuronal cell death? J Neurosci Res 79:231–239PubMedCrossRefGoogle Scholar
  126. 126.
    Lafon-Cazal M, Pietri S, Culcasi M, Bockaert J (1993) NMDA-dependent superoxide production and neurotoxicity. Nature 364:535–537PubMedCrossRefGoogle Scholar
  127. 127.
    Lipton SA, Choi YB, Pan ZH, Lei SZ, Chen HS, Sucher NJ, Loscalzo J, Singel DJ, Stamler JS (1993) A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature 364:626–632PubMedCrossRefGoogle Scholar
  128. 128.
    Yamauchi M, Omote K, Ninomiya T (1998) Direct evidence for the role of nitric oxide on the glutamate-induced neuronal death in cultured cortical neurons. Brain Res 780:253–259PubMedCrossRefGoogle Scholar
  129. 129.
    Leist M, Fava E, Montecucco C, Nicotera P (1997) Peroxynitrite and nitric oxide donors induce neuronal apoptosis by eliciting autocrine excitotoxicity. Eur J Neurosci 9:1488–1498PubMedCrossRefGoogle Scholar
  130. 130.
    Szatkowski M, Attwell D (1994) Triggering and execution of neuronal death in brain ischaemia: two phases of glutamate release by different mechanisms. Trends Neurosci 17:359–365PubMedCrossRefGoogle Scholar
  131. 131.
    Gasche Y, Soccal PM, Kanemitsu M, Copin JC (2006) Matrix metalloproteinases and diseases of the central nervous system with a special emphasis on ischemic brain. Front Biosci 11:1289–1301PubMedCrossRefGoogle Scholar
  132. 132.
    Lankiewicz S, Marc Luetjens C, Truc Bui N, Krohn AJ, Poppe M, Cole GM, Saido TC, Prehn JH (2000) Activation of calpain I converts excitotoxic neuron death into a caspase-independent cell death. J Biol Chem 275:17064–17071PubMedCrossRefGoogle Scholar
  133. 133.
    Wang KK (2000) Calpain and caspase: can you tell the difference? Trends Neurosci 23:20–26PubMedCrossRefGoogle Scholar
  134. 134.
    Neumar RW, Xu YA, Gada H, Guttmann RP, Siman R (2003) Cross-talk between calpain and caspase proteolytic systems during neuronal apoptosis. J Biol Chem 278:14162–14167PubMedCrossRefGoogle Scholar
  135. 135.
    Newcomb-Fernandez JK, Zhao X, Pike BR, Wang KK, Kampfl A, Beer R, DeFord SM, Hayes RL (2001) Concurrent assessment of calpain and caspase-3 activation after oxygen-glucose deprivation in primary septo-hippocampal cultures. J Cereb Blood Flow Metab 21:1281–1294PubMedCrossRefGoogle Scholar
  136. 136.
    Ray SK, Karmakar S, Nowak MW, Banik NL (2006) Inhibition of calpain and caspase-3 prevented apoptosis and preserved electrophysiological properties of voltage-gated and ligand-gated ion channels in rat primary cortical neurons exposed to glutamate. Neuroscience 139:577–595PubMedCrossRefGoogle Scholar
  137. 137.
    Robles E, Huttenlocher A, Gomez TM (2003) Filopodial calcium transients regulate growth cone motility and guidance through local activation of calpain. Neuron 38:597–609PubMedCrossRefGoogle Scholar
  138. 138.
    Das A, Sribnick EA, Wingrave JM, Del Re AM, Woodward JJ, Appel SH, Banik NL, Ray SK (2005) Calpain activation in apoptosis of ventral spinal cord 4.1 (VSC4.1) motoneurons exposed to glutamate: calpain inhibition provides functional neuroprotection. J Neurosci Res 81:551–562PubMedCrossRefGoogle Scholar
  139. 139.
    Takano J, Tomioka M, Tsubuki S, Higuchi M, Iwata N, Itohara S, Maki M, Saido TC (2005) Calpain mediates excitotoxic DNA fragmentation via mitochondrial pathways in adult brains: evidence from calpastatin mutant mice. J Biol Chem 280:16175–16184PubMedCrossRefGoogle Scholar
  140. 140.
    Van den Bosch L, Van Damme P, Vleminckx V, Van Houtte E, Lemmens G, Missiaen L, Callewaert G, Robberecht W (2002) An alpha-mercaptoacrylic acid derivative (PD150606) inhibits selective motor neuron death via inhibition of kainate-induced Ca2+ influx and not via calpain inhibition. Neuropharmacology 42:706–713PubMedCrossRefGoogle Scholar
  141. 141.
    Bahr BA, Bendiske J, Brown QB, Munirathinam S, Caba E, Rudin M, Urwyler S, Sauter A, Rogers G (2002) Survival signaling and selective neuroprotection through glutamatergic transmission. Exp Neurol 174:37–47PubMedCrossRefGoogle Scholar
  142. 142.
    Bizat N, Hermel JM, Humbert S, Jacquard C, Créminon C, Escartin C, Saudou F, Krajewski S, Hantraye P, Brouillet E (2003) In vivo calpain/caspase cross-talk during 3-nitropropionic acid-induced striatal degeneration: implication of a calpain-mediated cleavage of active caspase-3. J Biol Chem 278:43245–43253PubMedCrossRefGoogle Scholar
  143. 143.
    Reimertz C, Kögel D, Lankiewicz S, Poppe M, Prehn JH (2001) Ca(2+)-induced inhibition of apoptosis in human SH-SY5Y neuroblastoma cells: degradation of apoptotic protease activating factor-1 (APAF-1). J Neurochem 78:1256–1266PubMedCrossRefGoogle Scholar
  144. 144.
    Choi WS, Lee EH, Chung CW, Jung YK, Jin BK, Kim SU, Oh TH, Saido TC, Oh YJ (2001) Cleavage of Bax is mediated by caspase-dependent or -independent calpain activation in dopaminergic neuronal cells: protective role of Bcl-2. J Neurochem 77:1531–1541PubMedCrossRefGoogle Scholar
  145. 145.
    Gao G, Dou QP (2000) N-terminal cleavage of bax by calpain generates a potent proapoptotic 18-kDa fragment that promotes bcl-2-independent cytochrome C release and apoptotic cell death. J Cell Biochem 80:53–72PubMedCrossRefGoogle Scholar
  146. 146.
    Chen M, He H, Zhan S, Krajewski S, Reed JC, Gottlieb RA (2001) Bid is cleaved by calpain to an active fragment in vitro and during myocardial ischemia/reperfusion. J Biol Chem 276:30724–30728PubMedCrossRefGoogle Scholar
  147. 147.
    Gil-Parrado S, Fernández-Montalván A, Assfalg-Machleidt I, Popp O, Bestvater F, Holloschi A, Knoch TA, Auerswald EA, Welsh K, Reed JC, Fritz H, Fuentes-Prior P, Spiess E, Salvesen GS, Machleidt W (2002) Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family members. J Biol Chem 277:27217–27226PubMedCrossRefGoogle Scholar
  148. 148.
    Mandic A, Viktorsson K, Strandberg L, Heiden T, Hansson J, Linder S, Shoshan MC (2002) Calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis. Mol Cell Biol 22:3003–3013PubMedCrossRefGoogle Scholar
  149. 149.
    Atencio IA, Ramachandra M, Shabram P, Demers GW (2000) Calpain inhibitor 1 activates p53-dependent apoptosis in tumor cell lines. Cell Growth Differ 11:247–253PubMedGoogle Scholar
  150. 150.
    Danial NN, Korsmeyer SJ (2004) Cell death: critical control points. Cell 116:205–219PubMedCrossRefGoogle Scholar
  151. 151.
    Eldadah BA, Faden AI (2000) Caspase pathways, neuronal apoptosis, and CNS injury. J Neurotrauma 17:811–829PubMedCrossRefGoogle Scholar
  152. 152.
    Du Y, Bales KR, Dodel RC, Hamilton-Byrd E, Horn JW, Czilli DL, Simmons LK, Ni B, Paul SM (1997) Activation of a caspase 3-related cysteine protease is required for glutamate-mediated apoptosis of cultured cerebellar granule neurons. Proc Natl Acad Sci USA 94:11657–11662PubMedCrossRefGoogle Scholar
  153. 153.
    Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, Robertson N, Armstrong RC, Wang L, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES (1996) The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32. J Biol Chem 271:27099–27106PubMedCrossRefGoogle Scholar
  154. 154.
    Ha JS, Park SS (2006) Glutamate-induced oxidative stress, but not cell death, is largely dependent upon extracellular calcium in mouse neuronal HT22 cells. Neurosci Lett 393:165–169PubMedCrossRefGoogle Scholar
  155. 155.
    van Leyen K, Siddiq A, Ratan RR, Lo EH (2005) Proteasome inhibition protects HT22 neuronal cells from oxidative glutamate toxicity. J Neurochem 92:824–830PubMedCrossRefGoogle Scholar
  156. 156.
    Liu X, Kim CN, Pohl J, Wang X (1996) Purification and characterization of an interleukin-1beta-converting enzyme family protease that activates cysteine protease P32 (CPP32). J Biol Chem 271:13371–13376PubMedCrossRefGoogle Scholar
  157. 157.
    Satoh MS, Lindahl T (1992) Role of poly(ADP-ribose) formation in DNA repair. Nature 356:356–358PubMedCrossRefGoogle Scholar
  158. 158.
    Han Z, Malik N, Carter T, Reeves WH, Wyche JH, Hendrickson EA (1996) DNA-dependent protein kinase is a target for a CPP32-like apoptotic protease. J Biol Chem 271:25035–25040PubMedCrossRefGoogle Scholar
  159. 159.
    Hugunin M, Quintal LJ, Mankovich JA, Ghayur T (1996) Protease activity of in vitro transcribed and translated Caenorhabditis elegans cell death gene (ced-3) product. J Biol Chem 271:3517–3522PubMedCrossRefGoogle Scholar
  160. 160.
    Wang X, Zelenski NG, Yang J, Sakai J, Brown MS, Goldstein JL (1996) Cleavage of sterol regulatory element binding proteins (SREBPs) by CPP32 during apoptosis. EMBO J 15:1012–1020PubMedGoogle Scholar
  161. 161.
    Mashima T, Naito M, Noguchi K, Miller DK, Nicholson DW, Tsuruo T (1997) Actin cleavage by CPP-32/apopain during the development of apoptosis. Oncogene 14:1007–1012PubMedCrossRefGoogle Scholar
  162. 162.
    Finkbeiner S, Greenberg ME (1996) Ca(2+)-dependent routes to Ras: mechanisms for neuronal survival, differentiation, and plasticity? Neuron 16:233–236PubMedCrossRefGoogle Scholar
  163. 163.
    Lev S, Moreno H, Martinez R, Canoll P, Peles E, Musacchio JM, Plowman GD, Rudy B, Schlessinger J (1995) Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions. Nature 376:737–745PubMedCrossRefGoogle Scholar
  164. 164.
    Marshall CJ (1995) Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell 80:179–185PubMedCrossRefGoogle Scholar
  165. 165.
    Fukunaga K, Miyamoto E (1998) Role of MAP kinase in neurons. Mol Neurobiol 16:79–95PubMedCrossRefGoogle Scholar
  166. 166.
    Arendt T, Holzer M, Grossmann A, Zedlick D, Brückner MK (1995) Increased expression and subcellular translocation of the mitogen activated protein kinase kinase and mitogen-activated protein kinase in Alzheimer’s disease. Neuroscience 68:5–18PubMedCrossRefGoogle Scholar
  167. 167.
    Hu BR, Wieloch T (1994) Tyrosine phosphorylation and activation of mitogen-activated protein kinase in the rat brain following transient cerebral ischemia. J Neurochem 62:1357–1367PubMedCrossRefGoogle Scholar
  168. 168.
    Jiang Q, Gu Z, Zhang G, Jing G (2000) Diphosphorylation and involvement of extracellular signal-regulated kinases (ERK1/2) in glutamate-induced apoptotic-like death in cultured rat cortical neurons. Brain Res 857:71–77PubMedCrossRefGoogle Scholar
  169. 169.
    Tanaka K, Nogawa S, Nagata E, Ito D, Suzuki S, Dembo T, Kosakai A, Fukuuchi Y (2000) Persistent CREB phosphorylation with protection of hippocampal CA1 pyramidal neurons following temporary occlusion of the middle cerebral artery in the rat. Exp Neurol 161:462–471PubMedCrossRefGoogle Scholar
  170. 170.
    Irving EA, Barone FC, Reith AD, Hadingham SJ, Parsons AA (2000) Differential activation of MAPK/ERK and p38/SAPK in neurones and glia following focal cerebral ischaemia in the rat. Brain Res Mol Brain Res 77:65–75PubMedCrossRefGoogle Scholar
  171. 171.
    Giordano G, Sánchez-Pérez AM, Montoliu C, Berezney R, Malyavantham K, Costa LG, Calvete JJ, Felipo V (2005) Activation of NMDA receptors induces protein kinase A-mediated phosphorylation and degradation of matrin 3. Blocking these effects prevents NMDA-induced neuronal death. J Neurochem 94:808–818PubMedCrossRefGoogle Scholar
  172. 172.
    Kimura K, Kodama A, Hayasaka Y, Ohta T (2004) Activation of the cAMP/PKA signaling pathway is required for post-ecdysial cell death in wing epidermal cells of Drosophila melanogaster. Development 131:1597–1606PubMedCrossRefGoogle Scholar
  173. 173.
    Takano H, Sugimura M, Kanazawa Y, Uchida T, Morishima Y, Shirasaki Y (2004) Protective effect of DY-9760e, a calmodulin antagonist, against neuronal cell death. Biol Pharm Bull 27:1788–1791PubMedCrossRefGoogle Scholar
  174. 174.
    Ginnan R, Pfleiderer PJ, Pumiglia K, Singer HA (2004) PKC-delta and CaMKII-delta 2 mediate ATP-dependent activation of ERK1/2 in vascular smooth muscle. Am J Physiol Cell Physiol 286:C1281–C1289PubMedCrossRefGoogle Scholar
  175. 175.
    Zhai H, Nakade K, Oda M, Mitsumoto Y, Akagi M, Sakurai J, Fukuyama Y (2005) Honokiol-induced neurite outgrowth promotion depends on activation of extracellular signal-regulated kinases (ERK1/2). Eur J Pharmacol 516:112–117PubMedCrossRefGoogle Scholar
  176. 176.
    Lobner D, Canzoniero LM, Manzerra P, Gottron F, Ying H, Knudson M, Tian M, Dugan LL, Kerchner GA, Sheline CT, Korsmeyer SJ, Choi DW (2000) Zinc-induced neuronal death in cortical neurons. Cell Mol Biol (Noisy-le-grand) 46:797–806Google Scholar
  177. 177.
    Manzerra P, Behrens MM, Canzoniero LM, Wang XQ, Heidinger V, Ichinose T, Yu SP, Choi DW (2001) Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity. Proc Natl Acad Sci USA 98:11055–11061PubMedCrossRefGoogle Scholar
  178. 178.
    Choi JS, Kim HY, Chung JW, Chun MH, Kim SY, Yoon SH, Lee MY (2005) Activation of Src tyrosine kinase in microglia in the rat hippocampus following transient forebrain ischemia. Neurosci Lett 380:1–5PubMedCrossRefGoogle Scholar
  179. 179.
    Aikawa R, Komuro I, Yamazaki T, Zou Y, Kudoh S, Tanaka M, Shiojima I, Hiroi Y, Yazaki Y (1997) Oxidative stress activates extracellular signal-regulated kinases through Src and Ras in cultured cardiac myocytes of neonatal rats. J Clin Invest 100:1813–1821PubMedCrossRefGoogle Scholar
  180. 180.
    Naor Z, Benard O, Seger R (2000) Activation of MAPK cascades by G-protein-coupled receptors: the case of gonadotropin-releasing hormone receptor. Trends Endocrinol Metab 11:91–99PubMedCrossRefGoogle Scholar
  181. 181.
    Chung KC, Sung JY, Ahn W, Rhim H, Oh TH, Lee MG, Ahn YS (2001) Intracellular calcium mobilization induces immediate early gene pip92 via Src and mitogen-activated protein kinase in immortalized hippocampal cells. J Biol Chem 276:2132–2138PubMedGoogle Scholar
  182. 182.
    Liu Y, Zhang G, Gao C, Hou X (2001) NMDA receptor activation results in tyrosine phosphorylation of NMDA receptor subunit 2A(NR2A) and interaction of Pyk2 and Src with NR2A after transient cerebral ischemia and reperfusion. Brain Res 909:51–58PubMedCrossRefGoogle Scholar
  183. 183.
    Kaltschmidt C, Kaltschmidt B, Baeuerle PA (1995) Stimulation of ionotropic glutamate receptors activates transcription factor NF-kappa B in primary neurons. Proc Natl Acad Sci USA 92:9618–9622PubMedCrossRefGoogle Scholar
  184. 184.
    de Erausquin GA, Hyrc K, Dorsey DA, Mamah D, Dokucu M, Mascó DH, Walton T, Dikranian K, Soriano M, García Verdugo JM, Goldberg MP, Dugan LL (2003) Nuclear translocation of nuclear transcription factor-kappa B by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons. Mol Pharmacol 63:784–790PubMedCrossRefGoogle Scholar
  185. 185.
    Nakai M, Qin ZH, Chen JF, Wang Y, Chase TN (2000) Kainic acid-induced apoptosis in rat striatum is associated with nuclear factor-kappaB activation. J Neurochem 74:647–658PubMedCrossRefGoogle Scholar
  186. 186.
    Qin ZH, Wang Y, Chen RW, Wang X, Ren M, Chuang DM, Chase TN (2001) Prostaglandin A(1) protects striatal neurons against excitotoxic injury in rat striatum. J Pharmacol Exp Ther 297:78–87PubMedGoogle Scholar
  187. 187.
    Qin ZH, Wang Y, Nakai M, Chase TN (1998) Nuclear factor-kappa B contributes to excitotoxin-induced apoptosis in rat striatum. Mol Pharmacol 53:33–42PubMedGoogle Scholar
  188. 188.
    Zou J, Crews F (2006) CREB and NF-kappaB transcription factors regulate sensitivity to excitotoxic and oxidative stress induced neuronal cell death. Cell Mol Neurobiol 26:385–405PubMedCrossRefGoogle Scholar
  189. 189.
    Grilli M, Pizzi M, Memo M, Spano P (1996) Neuroprotection by aspirin and sodium salicylate through blockade of NF-kappaB activation. Science 274:1383–1385PubMedCrossRefGoogle Scholar
  190. 190.
    Nijboer CH, Heijnen CJ, Groenendaal F, May MJ, van Bel F, Kavelaars A (2008) Strong neuroprotection by inhibition of NF-kappaB after neonatal hypoxia-ischemia involves apoptotic mechanisms but is independent of cytokines. Stroke 39:2129–2137PubMedCrossRefGoogle Scholar
  191. 191.
    Panikashvili D, Mechoulam R, Beni SM, Alexandrovich A, Shohami E (2005) CB1 cannabinoid receptors are involved in neuroprotection via NF-kappa B inhibition. J Cereb Blood Flow Metab 25:477–484PubMedCrossRefGoogle Scholar
  192. 192.
    Uberti D, Carsana T, Francisconi S, Ferrari Toninelli G, Canonico PL, Memo M (2004) A novel mechanism for pergolide-induced neuroprotection: inhibition of NF-kappaB nuclear translocation. Biochem Pharmacol 67:1743–5170PubMedCrossRefGoogle Scholar
  193. 193.
    Casper D, Yaparpalvi U, Rempel N, Werner P (2000) Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro. Neurosci Lett 289:201–204PubMedCrossRefGoogle Scholar
  194. 194.
    Cherng JM, Lin HJ, Hung MS, Lin YR, Chan MH, Lin JC (2006) Inhibition of nuclear factor kappaB is associated with neuroprotective effects of glycyrrhizic acid on glutamate-induced excitotoxicity in primary neurons. Eur J Pharmacol 547:10–21PubMedCrossRefGoogle Scholar
  195. 195.
    Vernon AC, Croucher MJ, Dexter DT (2008) Additive neuroprotection by metabotropic glutamate receptor subtype-selective ligands in a rat Parkinson’s model. Neuroreport 19:475–478PubMedCrossRefGoogle Scholar
  196. 196.
    Vernon AC, Palmer S, Datla KP, Zbarsky V, Croucher MJ, Dexter DT (2005) Neuroprotective effects of metabotropic glutamate receptor ligands in a 6-hydroxydopamine rodent model of Parkinson’s disease. Eur J Neurosci 22:1799–1806PubMedCrossRefGoogle Scholar
  197. 197.
    Shaulian E, Karin M (2002) AP-1 as a regulator of cell life and death. Nat Cell Biol 4:E131–E136PubMedCrossRefGoogle Scholar
  198. 198.
    Behrens A, Sibilia M, Wagner EF (1999) Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation. Nat Genet 21:326–329PubMedCrossRefGoogle Scholar
  199. 199.
    Borsello T, Clarke PG, Hirt L, Vercelli A, Repici M, Schorderet DF, Bogousslavsky J, Bonny C (2003) A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia. Nat Med 9:1180–1186PubMedCrossRefGoogle Scholar
  200. 200.
    Yang DD, Kuan CY, Whitmarsh AJ, Rincón M, Zheng TS, Davis RJ, Rakic P, Flavell RA (1997) Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature 389:865–870PubMedCrossRefGoogle Scholar
  201. 201.
    Bading H, Ginty DD, Greenberg ME (1993) Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways. Science 260:181–186PubMedCrossRefGoogle Scholar
  202. 202.
    Greenberg ME, Ziff EB, Greene LA (1986) Stimulation of neuronal acetylcholine receptors induces rapid gene transcription. Science 234:80–83PubMedCrossRefGoogle Scholar
  203. 203.
    Griffiths R, Grieve A, Scollon J, Scott M, Williams C, Meredith C (2000) Preliminary evaluation of an in vitro test for assessment of excitotoxicity by measurement of early gene (c-fos mRNA) levels. Toxicol In Vitro 14:447–458PubMedCrossRefGoogle Scholar
  204. 204.
    Griffiths R, Malcolm C, Ritchie L, Frandsen A, Schousboe A, Scott M, Rumsby P, Meredith C (1997) Association of c-fos mRNA expression and excitotoxicity in primary cultures of mouse neocortical and cerebellar neurons. J Neurosci Res 48:533–542PubMedCrossRefGoogle Scholar
  205. 205.
    Shehadeh J, Fernandes HB, Zeron Mullins MM, Graham RK, Leavitt BR, Hayden MR, Raymond LA (2006) Striatal neuronal apoptosis is preferentially enhanced by NMDA receptor activation in YAC transgenic mouse model of Huntington disease. Neurobiol Dis 21:392–403PubMedCrossRefGoogle Scholar
  206. 206.
    Zeron MM, Fernandes HB, Krebs C, Shehadeh J, Wellington CL, Leavitt BR, Baimbridge KG, Hayden MR, Raymond LA (2004) Potentiation of NMDA receptor-mediated excitotoxicity linked with intrinsic apoptotic pathway in YAC transgenic mouse model of Huntington’s disease. Mol Cell Neurosci 25:469–479PubMedCrossRefGoogle Scholar
  207. 207.
    Coyle JT, Schwarcz R (1976) Lesion of striatal neurons with kainic acid provides a model for Huntington’s chorea. Nature 263:244–246PubMedCrossRefGoogle Scholar
  208. 208.
    Roberts RC, Du E, McCarthy KE, Okuno E, Schwartz R (1992) Immunocytochemical localization of kynurenine aminotransferase in the rat striatum: a light and electron microscopic study. J Comp Neurol 326:82–90PubMedCrossRefGoogle Scholar
  209. 209.
    Benn CL, Slow EJ, Farrell LA, Graham R, Deng Y, Hayden MR, Cha JH (2007) Glutamate receptor abnormalities in the YAC128 transgenic mouse model of Huntington’s disease. Neuroscience 147:354–372PubMedCrossRefGoogle Scholar
  210. 210.
    Schiefer J, Sprünken A, Puls C, Lüesse HG, Milkereit A, Milkereit E, Johann V, Kosinski CM (2004) The metabotropic glutamate receptor 5 antagonist MPEP and the mGluR2 agonist LY379268 modify disease progression in a transgenic mouse model of Huntington’s disease. Brain Res 1019:246–254PubMedCrossRefGoogle Scholar
  211. 211.
    Fan MM, Raymond LA (2007) N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington’s disease. Prog Neurobiol 81:272–293PubMedCrossRefGoogle Scholar
  212. 212.
    Sun Y, Savanenin A, Reddy PH, Liu YF (2001) Polyglutamine-expanded huntingtin promotes sensitization of N-methyl-D-aspartate receptors via post-synaptic density 95. J Biol Chem 276:24713–24718PubMedCrossRefGoogle Scholar
  213. 213.
    Song C, Zhang Y, Parsons CG, Liu YF (2003) Expression of polyglutamine-expanded huntingtin induces tyrosine phosphorylation of N-methyl-D-aspartate receptors. J Biol Chem 278:33364–33369PubMedCrossRefGoogle Scholar
  214. 214.
    Jarabek BR, Yasuda RP, Wolfe BB (2004) Regulation of proteins affecting NMDA receptor-induced excitotoxicity in a Huntington’s mouse model. Brain 127:505–516PubMedCrossRefGoogle Scholar
  215. 215.
    Beal MF (2009) Mitochondrial dysfunction in neurodegenerative diseases and stroke: neuroprotective strategies. J Neurol Sci 283:240CrossRefGoogle Scholar
  216. 216.
    Keating DJ (2008) Mitochondrial dysfunction, oxidative stress, regulation of exocytosis and their relevance to neurodegenerative diseases. J Neurochem 104:298–305PubMedGoogle Scholar
  217. 217.
    Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795PubMedCrossRefGoogle Scholar
  218. 218.
    Del Río P, Montiel T, Chagoya V, Massieu L (2007) Exacerbation of excitotoxic neuronal death induced during mitochondrial inhibition in vivo: relation to energy imbalance or ATP depletion? Neuroscience 146:1561–1570PubMedCrossRefGoogle Scholar
  219. 219.
    García O, Massieu L (2001) Strategies for neuroprotection against L-trans-2,4-pyrrolidine dicarboxylate-induced neuronal damage during energy impairment in vitro. J Neurosci Res 64:418–428PubMedCrossRefGoogle Scholar
  220. 220.
    Mejía-Toiber J, Montiel T, Massieu L (2006) D-beta-hydroxybutyrate prevents glutamate-mediated lipoperoxidation and neuronal damage elicited during glycolysis inhibition in vivo. Neurochem Res 31:1399–1408PubMedCrossRefGoogle Scholar
  221. 221.
    Camacho A, Montiel T, Massieu L (2007) Sustained metabolic inhibition induces an increase in the content and phosphorylation of the NR2B subunit of N-methyl-D-aspartate receptors and a decrease in glutamate transport in the rat hippocampus in vivo. Neuroscience 145:873–886PubMedCrossRefGoogle Scholar
  222. 222.
    Arias C, Montiel T, Quiroz-Báez R, Massieu L (2002) β-Amyloid neurotoxicity is exacerbated during glycolysis inhibition and mitochondrial impairment in the rat hippocampus in vivo and in isolated nerve terminals: implications for Alzheimer’s disease. Exp Neurol 176:163–174PubMedCrossRefGoogle Scholar
  223. 223.
    Grewer C, Gameiro A, Zhang Z, Tao Z, Braams S, Rauen T (2008) Glutamate forward and reverse transport: from molecular mechanism to transporter-mediated release after ischemia. IUBMB Life 60:609–619PubMedCrossRefGoogle Scholar
  224. 224.
    Billups B, Attwell D (1996) Modulation of non-vesicular glutamate release by pH. Nature 379:171–174PubMedCrossRefGoogle Scholar
  225. 225.
    Jabaudon D, Scanziani M, Gähwiler BH, Gerber U (2000) Acute decrease in net glutamate uptake during energy deprivation. Proc Natl Acad Sci USA 97:5610–5615PubMedCrossRefGoogle Scholar
  226. 226.
    Esslinger CS, Agarwal S, Gerdes J, Wilson PA, Davis ES, Awes AN, O’Brien E, Mavencamp T, Koch HP, Poulsen DJ, Rhoderick JF, Chamberlin AR, Kavanaugh MP, Bridges RJ (2005) The substituted aspartate analogue L-beta-threo-benzyl-aspartate preferentially inhibits the neuronal excitatory amino acid transporter EAAT3. Neuropharmacology 49:850–861PubMedCrossRefGoogle Scholar
  227. 227.
    Rossi DJ, Brady JD, Mohr C (2007) Astrocyte metabolism and signaling during brain ischemia. Nat Neurosci 10:1377–1386PubMedCrossRefGoogle Scholar
  228. 228.
    Auger C, Attwell D (2000) Fast removal of synaptic glutamate by postsynaptic transporters. Neuron 28:547–558PubMedCrossRefGoogle Scholar
  229. 229.
    Yamashita A, Makita K, Kuroiwa T, Tanaka K (2006) Glutamate transporters GLAST and EAAT4 regulate postischemic Purkinje cell death: an in vivo study using a cardiac arrest model in mice lacking GLAST or EAAT4. Neurosci Res 55:264–270PubMedCrossRefGoogle Scholar
  230. 230.
    Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105PubMedCrossRefGoogle Scholar
  231. 231.
    O’Shea RD (2002) Roles and regulation of glutamate transporters in the central nervous system. Clin Exp Pharmacol Physiol 29:1018–1023PubMedCrossRefGoogle Scholar
  232. 232.
    Arriza JL, Eliasof S, Kavanaugh MP, Amara SG (1997) Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc Natl Acad Sci USA 94:4155–4160PubMedCrossRefGoogle Scholar
  233. 233.
    Hu WH, Walters WM, Xia XM, Karmally SA, Bethea JR (2003) Neuronal glutamate transporter EAAT4 is expressed in astrocytes. Glia 44:13–25PubMedCrossRefGoogle Scholar
  234. 234.
    Bridges RJ, Esslinger CS (2005) The excitatory amino acid transporters: pharmacological insights on substrate and inhibitor specificity of the EAAT subtypes. Pharmacol Ther 107:271–285PubMedCrossRefGoogle Scholar
  235. 235.
    Campiani G, Fattorusso C, De Angelis M, Catalanotti B, Butini S, Fattorusso R, Fiorini I, Nacci V, Novellino E (2003) Neuronal high-affinity sodium-dependent glutamate transporters (EAATs): targets for the development of novel therapeutics against neurodegenerative diseases. Curr Pharm Des 9:599–625PubMedCrossRefGoogle Scholar
  236. 236.
    Dugan LL, Bruno VMG, Amagasu SM, Giffard RG (1995) Glia modulate the response of murine cortical neurons to excitotoxicity: glia exacerbate AMPA neurotoxicity. J Neurosci 15:4545–4555PubMedGoogle Scholar
  237. 237.
    Guiramand J, Martin A, de Jesus Ferreira MC, Cohen-Solal C, Vignes M, Récasens M (2005) Gliotoxicity in hippocampal cultures is induced by transportable, but not by nontransportable, glutamate uptake inhibitors. J Neurosci Res 81:199–207PubMedCrossRefGoogle Scholar
  238. 238.
    Bonde C, Noraberg J, Noer H, Zimmer J (2005) Ionotropic glutamate receptors and glutamate transporters are involved in necrotic neuronal cell death induced by oxygen-glucose deprivation of hippocampal slice cultures. Neuroscience 136:779–794PubMedCrossRefGoogle Scholar
  239. 239.
    Selkirk JV, Nottebaum LM, Vana AM, Verge GM, Mackay KB, Stiefel TH, Naeve GS, Pomeroy JE, Petroski RE, Moyer J, Dunlop J, Foster AC (2005) Role of the GLT-1 subtype of glutamate transporter in glutamate homeostasis: the GLT-1-preferring inhibitor WAY-855 produces marginal neurotoxicity in the rat hippocampus. Eur J Neurosci 21:3217–3228PubMedCrossRefGoogle Scholar
  240. 240.
    Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, Kanai Y, Hediger M, Wang Y, Schielke JP, Welty DF (1996) Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16:675–686PubMedCrossRefGoogle Scholar
  241. 241.
    Tanaka K, Watase K, Manabe T, Yamada K, Watanabe M, Takahashi K, Iwama H, Nishikawa T, Ichihara N, Kikuchi T, Okuyama S, Kawashima N, Hori S, Takimoto M, Wada K (1997) Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science 276:1699–1702PubMedCrossRefGoogle Scholar
  242. 242.
    Barger SW, Basile AS (2001) Activation of microglia by secreted amyloid precursor protein evokes release of glutamate by cystine exchange and attenuates synaptic function. J Neurochem 76:846–854PubMedCrossRefGoogle Scholar
  243. 243.
    Barger SW, Goodwin ME, Porter MM, Beggs ML (2007) Glutamate release from activated microglia requires the oxidative burst and lipid peroxidation. J Neurochem 101:1205–1213PubMedCrossRefGoogle Scholar
  244. 244.
    Takeuchi H, Mizuno T, Zhang G, Wang J, Kawanokuchi J, Kuno R, Suzumura A (2005) Neuritic beading induced by activated microglia is an early feature of neuronal dysfunction toward neuronal death by inhibition of mitochondrial respiration and axonal transport. J Biol Chem 280:10444–10454PubMedCrossRefGoogle Scholar
  245. 245.
    Pekny M, Nilsson M (2005) Astrocyte activation and reactive gliosis. Glia 50:427–434PubMedCrossRefGoogle Scholar
  246. 246.
    Takeuchi H, Jin S, Wang J, Zhang G, Kawanokuchi J, Kuno R, Sonobe Y, Mizuno T, Suzumura A (2006) Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J Biol Chem 281:21362–21368PubMedCrossRefGoogle Scholar
  247. 247.
    Domercq M, Sánchez-Gómez MV, Sherwin C, Etxebarria E, Fern R, Matute C (2007) System xc- and glutamate transporter inhibition mediates microglial toxicity to oligodendrocytes. J Immunol 178:6549–6556PubMedGoogle Scholar
  248. 248.
    Tzingounis AV, Wadiche JI (2007) Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nat Rev Neurosci 8:935–947PubMedCrossRefGoogle Scholar
  249. 249.
    McIlvain HB, She Y, Howland DS, Dunlop J (2008) Synaptosomal glutamate transport studies in a transgenic rat model of amyotrophic lateral sclerosis. J Neurochem 81:60–63CrossRefGoogle Scholar
  250. 250.
    Behrens PF, Franz P, Woodman B, Lindenberg KS, Landwehrmeyer GB (2002) Impaired glutamate transport and glutamate-glutamine cycling: downstream effects of the Huntington mutation. Brain 125:1908–1922PubMedCrossRefGoogle Scholar
  251. 251.
    Estrada-Sánchez AM, Montiel T, Segovia J, Massieu L (2009) Glutamate toxicity in the striatum of the R6/2 Huntington’s disease transgenic mice is age-dependent and correlates with decreased levels of glutamate transporters. Neurobiol Dis 34:78–86PubMedCrossRefGoogle Scholar
  252. 252.
    Kashani A, Betancur C, Giros B, Hirsch E, El Mestikawy S (2007) Altered expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in Parkinson disease. Neurobiol Aging 28:568–578PubMedCrossRefGoogle Scholar
  253. 253.
    Jacob CP, Koutsilieri E, Bartl J, Neuen-Jacob E, Arzberger T, Zander N, Ravid R, Roggendorf W, Riederer P, Grünblatt E (2007) Alterations in expression of glutamatergic transporters and receptors in sporadic Alzheimer’s disease. J Alzheimers Dis 11:97–116PubMedGoogle Scholar
  254. 254.
    Sultana R, Butterfield DA (2008) Alterations of some membrane transport proteins in Alzheimer’s disease: role of amyloid beta-peptide. Mol Biosyst 4:36–41PubMedCrossRefGoogle Scholar
  255. 255.
    Antonelli T, Tomasini MC, Fuxe K, Agnati LF, Tanganelli S, Ferraro L (2007) Receptor-receptor interactions as studied with microdialysis. Focus on NTR/D2 interactions in the basal ganglia. J Neural Transm 114:105–113PubMedCrossRefGoogle Scholar
  256. 256.
    Dobner PR, Deutch AY, Fadel J (2003) Neurotensin: dual roles in psychostimulant and antipsychotic drug responses. Life Sci 73:801–811PubMedCrossRefGoogle Scholar
  257. 257.
    Petrie KA, Schmidt D, Bubser M, Fadel J, Carraway RE, Deutch AY (2005) Neurotensin activates GABAergic interneurons in the prefrontal cortex. J Neurosci 25:1629–1636PubMedCrossRefGoogle Scholar
  258. 258.
    St-Gelais F, Jomphe C, Trudeau LE (2006) The role of neurotensin in central nervous system pathophysiology: what is the evidence? J Psychiatry Neurosci 31:229–245PubMedGoogle Scholar
  259. 259.
    Antonelli T, Ferraro L, Fuxe K, Finetti S, Fournier J, Tanganelli S, De Mattei M, Tomasini MC (2004) Neurotensin enhances endogenous extracellular glutamate levels in primary cultures of rat cortical neurons: involvement of neurotensin receptor in NMDA induced excitotoxicity. Cereb Cortex 14:466–473PubMedCrossRefGoogle Scholar
  260. 260.
    Antonelli T, Tomasini MC, Finetti S, Giardino L, Calzà L, Fuxe K, Soubriè P, Tanganelli S, Ferraro L (2002) Neurotensin enhances glutamate excitotoxicity in mesencephalic neurons in primary culture. J Neurosci Res 70:766–773PubMedCrossRefGoogle Scholar
  261. 261.
    Silakova JM, Hewett JA, Hewett SJ (2004) Naproxen reduces excitotoxic neurodegeneration in vivo with an extended therapeutic window. J Pharmacol Exp Ther 309:1060–1066PubMedCrossRefGoogle Scholar
  262. 262.
    Mirjany M, Ho L, Pasinetti GM (2002) Role of cyclooxygenase-2 in neuronal cell cycle activity and glutamate-mediated excitotoxicity. J Pharmacol Exp Ther 301:494–500PubMedCrossRefGoogle Scholar
  263. 263.
    Iadecola C, Niwa K, Nogawa S, Zhao X, Nagayama M, Araki E, Morham S, Ross ME (2001) Reduced susceptibility to ischemic brain injury and N-methyl-D-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice. Proc Natl Acad Sci USA 98:1294–1299PubMedCrossRefGoogle Scholar
  264. 264.
    Candelario-Jalil E, Ajamieh HH, Sam S, Martínez G, León Fernández OS (2000) Nimesulide limits kainate-induced oxidative damage in the rat hippocampus. Eur J Pharmacol 390:295–298PubMedCrossRefGoogle Scholar
  265. 265.
    Carlson NG (2003) Neuroprotection of cultured cortical neurons mediated by the cyclooxygenase-2 inhibitor APHS can be reversed by a prostanoid. J Neurosci Res 71:79–88PubMedCrossRefGoogle Scholar
  266. 266.
    McCullough L, Wu L, Haughey N, Liang X, Hand T, Wang Q, Breyer RM, Andreasson K (2004) Neuroprotective function of the PGE2 EP2 receptor in cerebral ischemia. J Neurosci 24:257–268PubMedCrossRefGoogle Scholar
  267. 267.
    Iadecola C, Forster C, Nogawa S, Clark HB, Ross ME (1999) Cyclooxygenase-2 immunoreactivity in the human brain following cerebral ischemia. Acta Neuropathol (Berl) 98:9–14CrossRefGoogle Scholar
  268. 268.
    Hoozemans JJ, Rozemuller AJ, Janssen I, De Groot CJ, Veerhuis R, Eikelenboom P (2001) Cyclooxygenase expression in microglia and neurons in Alzheimer’s disease and control brain. Acta Neuropathol 101:2–8PubMedGoogle Scholar
  269. 269.
    Teismann P, Tieu K, Choi DK, Wu DC, Naini A, Hunot S, Vila M, Jackson-Lewis V, Przedborski S (2003) Cyclooxygenase-2 is instrumental in Parkinson’s disease neurodegeneration. Proc Natl Acad Sci USA 100:5473–5478PubMedCrossRefGoogle Scholar
  270. 270.
    Yasojima K, Schwab C, McGeer EG, McGeer PL (1999) Distribution of cyclooxygenase-1 and cyclooxygenase-2 mRNAs and proteins in human brain and peripheral organs. Brain Res 830:226–236PubMedCrossRefGoogle Scholar
  271. 271.
    Yokota O, Terada S, Ishizu H, Ishihara T, Nakashima H, Kugo A, Tsuchiya K, Ikeda K, Hayabara T, Saito Y, Murayama S, Uéda K, Checler F, Kuroda S (2004) Increased expression of neuronal cyclooxygenase-2 in the hippocampus in amyotrophic lateral sclerosis both with and without dementia. Acta Neuropathol 107:399–405PubMedCrossRefGoogle Scholar
  272. 272.
    Candelario-Jalil E, González-Falcón A, García-Cabrera M, Alvarez D, Al-Dalain S, Martínez G, León OS, Springer JE (2003) 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 86:545–555PubMedCrossRefGoogle Scholar
  273. 273.
    Gopez JJ, Yue H, Vasudevan R, Malik AS, Fogelsanger LN, Lewis S, Panikashvili D, Shohami E, Jansen SA, Narayan RK, Strauss KI (2005) Cyclooxygenase-2-specific inhibitor improves functional outcomes, provides neuroprotection, and reduces inflammation in a rat model of traumatic brain injury. Neurosurgery 56:590–604PubMedCrossRefGoogle Scholar
  274. 274.
    Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ, Memantine Study Group (2003) Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med 348:1333–1341PubMedCrossRefGoogle Scholar
  275. 275.
    Hewett SJ, Silakova JM, Hewett JA (2006) Oral treatment with rofecoxib reduces hippocampal excitotoxic neurodegeneration. J Pharmacol Exp Ther 319:1219–1224PubMedCrossRefGoogle Scholar
  276. 276.
    Caumont AS, Octave JN, Hermans E (2006) Specific regulation of rat glial cell line-derived neurotrophic factor gene expression by riluzole in C6 glioma cells. J Neurochem 97:128–139PubMedCrossRefGoogle Scholar
  277. 277.
    Shortland PJ, Leinster VH, White W, Robson LG (2006) Riluzole promotes cell survival and neurite outgrowth in rat sensory neurones in vitro. Eur J Neurosci 24:3343–3353PubMedCrossRefGoogle Scholar
  278. 278.
    Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, Kalra S, Katz JS, Mitsumoto H, Rosenfeld J, Shoesmith C, Strong MJ, Woolley SC, Quality Standards Subcommittee of the American Academy of Neurology (2009) Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 73:1218–1226PubMedCrossRefGoogle Scholar
  279. 279.
    Del Signore SJ, Amante DJ, Kim J, Stack EC, Goodrich S, Cormier K, Smith K, Cudkowicz ME, Ferrante RJ (2009) Combined riluzole and sodium phenylbutyrate therapy in transgenic amyotrophic lateral sclerosis mice. Amyotroph Lateral Scler 10:85–94PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Pharmacology and Laboratory of Aging and Nervous Diseases (SZS0703)Soochow University School of MedicineSuzhouChina

Personalised recommendations