Transient P2X7 receptor antagonism produces lasting reductions in spontaneous seizures and gliosis in experimental temporal lobe epilepsy

Journal of Neuroscience

Volumn 36, Issue 22, 2016, Pages 5920-5932

  Jimenez Pacheco, Alba ^a   Diaz Hernandez, Miguel ^c   Arribas Blázquez, Marina ^c   Sanz Rodriguez, Amaya ^a   Olivos Oré, Luis A ^c   Artalejo, Antonio R ^c   Alves, Mariana ^a   Letavic, Michael ^d   Teresa Miras Portugal, M ^c   Conroy, Ronan M ^b   Delanty, Norman ^e   Farrell, Michael A ^e   O’Brien, Donncha F ^e   Bhattacharya, Anindya ^d   Engel, Tobias ^a   Henshall, David C ^a  

^a Department of Physiology and Medical Physics ^*  (Ireland)

^b ROYAL COLLEGE OF SURGEONS IN IRELAND   (Ireland)

^c UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^d JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^e BEAUMONT HOSPITAL   (Ireland)

Author keywords

Anticonvulsant; Hippocampal sclerosis; Inflammatory cytokine; Microglia; Purinergic receptor; Status epilepticus

Indexed keywords

INFLAMMASOME; INTERLEUKIN 1BETA; JNJ 47965567; LORAZEPAM; PURINERGIC P2X7 RECEPTOR; UNCLASSIFIED DRUG; 3'-O-(4-BENZOYL)BENZOYLADENOSINE 5'-TRIPHOSPHATE; ACTIN BINDING PROTEIN; ADENOSINE TRIPHOSPHATE; AIF1 PROTEIN, MOUSE; ANTITHROMBOCYTIC AGENT; CALCIUM BINDING PROTEIN; ENHANCED GREEN FLUORESCENT PROTEIN; GREEN FLUORESCENT PROTEIN; JNJ-47965567; NERVE PROTEIN; NICOTINAMIDE; PIPERAZINE DERIVATIVE; PURINERGIC P2X RECEPTOR ANTAGONIST;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ASTROCYTOSIS; AUTOPSY; BAC GENE; BRAIN ELECTROPHYSIOLOGY; BRAIN SYNAPTOSOME; CELL PROLIFERATION; CONTROLLED STUDY; EPIFLUORESCENCE MICROSCOPY; EPILEPTIC STATE; FOCAL EPILEPSY; GENE; GLIOSIS; HISTOPATHOLOGY; HUMAN; HUMAN TISSUE; IMMUNOFLUORESCENCE MICROSCOPY; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MALE; MOUSE; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NEUROLOGIC DISEASE; NONHUMAN; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; SEIZURE; TEMPORAL LOBE EPILEPSY; UPREGULATION; WESTERN BLOTTING; ADOLESCENT; ANALOGS AND DERIVATIVES; ANIMAL; BRAIN; C57BL MOUSE; COMPLICATION; DISEASE MODEL; DRUG EFFECTS; EPILEPSY, TEMPORAL LOBE; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MIDDLE AGED; PATHOLOGY; PHYSIOLOGY; SEIZURES; TRANSGENIC MOUSE; ULTRASTRUCTURE; YOUNG ADULT;

ADENOSINE TRIPHOSPHATE; ADOLESCENT; ADULT; ANIMALS; BRAIN; CALCIUM-BINDING PROTEINS; DISEASE MODELS, ANIMAL; EPILEPSY, TEMPORAL LOBE; GENE EXPRESSION REGULATION; GLIOSIS; GREEN FLUORESCENT PROTEINS; HUMANS; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MICROFILAMENT PROTEINS; MIDDLE AGED; NERVE TISSUE PROTEINS; NIACINAMIDE; PIPERAZINES; PLATELET AGGREGATION INHIBITORS; PURINERGIC P2X RECEPTOR ANTAGONISTS; RECEPTORS, PURINERGIC P2X7; SEIZURES; UP-REGULATION; YOUNG ADULT;

EID: 84971673307     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.4009-15.2016     Document Type: Article

References (70)

1. Abbracchio MP, Burnstock G, Verkhratsky A, Zimmermann H (2009) Purinergic signalling in the nervous system: an overview. Trend Neurosci 32:19-29
2. Allan SM, Tyrrell PJ, Rothwell NJ (2005) Interleukin-1 and neuronal injury. Nat Rev Immunol 5:629-640
3. Anderson CM, Nedergaard M (2006) Emerging challenges of assigning P2X7 receptor function and immunoreactivity in neurons. Trend Neurosci 29:257-262
4. Armstrong JN, Brust TB, Lewis RG, MacVicar BA (2002) Activation of pre-synaptic P2X7-like receptors depresses mossy fiber-CA3 synaptic transmission through p38 mitogen-activated protein kinase. J Neurosci 22: 5938-5945
5. Bhattacharya A, Wang Q, Ao H, Shoblock JR, Lord B, Aluisio L, Fraser I, Nepomuceno D, Neff RA, Welty N, Lovenberg TW, Bonaventure P, Wickenden AD, Letavic MA (2013) Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567. Br J Pharmacol 170:624-640
6. Bialer M, White HS (2010) Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov 9:68-82
7. Bianco F, Pravettoni E, Colombo A, Schenk U, Möller T, Matteoli M, Verderio C (2005) Astrocyte-derived ATP induces vesicle shedding and IL-1 beta release from microglia. J Immunol 174:7268-7277
8. Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: un-covering the molecular mechanisms. Nat Rev Neurosci 8:57-69
9. Burnstock G (2008) Purinergic signalling and disorders of the central ner-vous system. Nat Rev Drug Discov 7:575-590
10. Chakir A, Fabene PF, Ouazzani R, Bentivoglio M (2006) Drug resistance and hippocampal damage after delayed treatment of pilocarpine-induced epilepsy in the rat. Brain Res Bull 71:127-138
11. Devinsky O, Vezzani A, Najjar S, De Lanerolle NC, Rogawski MA (2013) Glia and epilepsy: excitability and inflammation. Trend Neurosci 36:174-184
12. Díaz-Hernández M, Pintor J, Castro E, Miras-Portugal MT (2001a) Independent receptors for diadenosine pentaphosphate and ATP in rat midbrain single synaptic terminals. Eur J Neurosci 14:918-926
13. Díaz-Hernández M, Gómez-Villafuertes R, Hernando F, Pintor J, Miras-Portugal MT (2001b) Presence of different ATP receptors on rat midbrain single synaptic terminals. Involvement of the P2X(3) subunits. Neurosci Lett 301:159-162
14. Doná F, Ulrich H, Persike DS, Conceição IM, Blini JP, Cavalheiro EA, Fernandes MJ (2009) Alteration of purinergic P2X4 and P2X7 receptor expression in rats with temporal-lobe epilepsy induced by pilocarpine. Epilepsy Res 83:157-167
15. Duan S, Anderson CM, Keung EC, Chen Y, Chen Y, Swanson RA (2003) P2X7 receptor-mediated release of excitatory amino acids from astrocytes. J Neurosci 23:1320-1328
16. Eltzschig HK, Sitkovsky MV, Robson SC (2013) Purinergic signaling during inflammation. N Engl J Med 368:1260
17. Engel T, Jimenez-Pacheco A, Miras-Portugal MT, Diaz-Hernandez M, Henshall DC (2012a) P2X7 receptor in epilepsy; role in pathophysiology and potential targeting for seizure control. Int J Physiol Pathophysiol Pharmacol 4:174-187
18. Engel T, Gomez-Villafuertes R, Tanaka K, Mesuret G, Sanz-Rodriguez A, Garcia-Huerta P, Miras-Portugal MT, Henshall DC, Diaz-Hernandez M (2012b) Seizure suppression and neuroprotection by targeting the purinergic P2X7 receptor during status epilepticus in mice. FASEB J 26:1616-1628
19. Engel T, Sanz-Rodgriguez A, Jimenez-Mateos EM, Concannon CG, Jimenez-Pacheco A, Moran C, Mesuret G, Petit E, Delanty N, Farrell MA, O’Brien DF, Prehn JH, Lucas JJ, Henshall DC (2013) CHOP regulates the p53-MDM2 axis and is required for neuronal survival after seizures. Brain 136:577-592
20. Fellin T, Pozzan T, Carmignoto G (2006) Purinergic receptors mediate two distinct glutamate release pathways in hippocampal astrocytes. J Biol Chem 281:4274-4284
21. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr, Forsgren L, French JA, Glynn M, Hesdorffer DC, Lee BI, Mathern GW, Moshé SL, Perucca E, Scheffer IE, Tomson T, Watanabe M, Wiebe S (2014) ILAE official report: a practical clinical definition of epilepsy. Epilepsia 55:475-482
22. Franceschini A, Capece M, Chiozzi P, Falzoni S, Sanz JM, Sarti AC, Bonora M, Pinton P, Di Virgilio F (2015) The P2X7 receptor directly interacts with the NLRP3 inflammasome scaffold protein. FASEB J 29:2450-2461
23. Grabenstatter HL, Clark S, Dudek FE (2007) Anticonvulsant effects of car-bamazepine on spontaneous seizures in rats with kainate-induced epilepsy: comparison of intraperitoneal injections with drug-in-food protocols. Epilepsia 48:2287-2295
24. Haydon PG, Carmignoto G (2006) Astrocyte control of synaptic transmis-sion and neurovascular coupling. Physiol Rev 86:1009-1031
25. Hirayama Y, Ikeda-Matsuo Y, Notomi S, Enaida H, Kinouchi H, Koizumi S (2015) Astrocyte-mediated ischemic tolerance. J Neurosci 35:3794-3805
26. Idzko M, Ferrari D, Eltzschig HK (2014) Nucleotide signalling during inflammation. Nature 509:310-317
27. Jabs R, Matthias K, Grote A, Grauer M, Seifert G, Steinhäuser C (2007) Lack of P2X receptor mediated currents in astrocytes and GluR type glial cells of the hippocampal CA1 region. Glia 55:1648-1655
28. Jabs R, Seifert G, Steinhäuser C (2008) Astrocytic function and its alteration in the epileptic brain. Epilepsia 49 [Suppl 2]:3-12
29. Jimenez-Mateos EM, Mouri G, Conroy RM, Henshall DC (2010) Epileptic tolerance is associated with enduring neuroprotection and uncoupling of the relationship between CA3 damage, neuropeptide Y rearrangement and spontaneous seizures following intra-amygdala kainic acid-induced status epilepticus in mice. Neuroscience 171:556-565
30. Jimenez-Mateos EM, Arribas-Blazquez M, Sanz-Rodriguez A, Concannon C, Olivos-Ore LA, Reschke CR, Mooney CM, Mooney C, Lugara E, Morgan J, Langa E, Jimenez-Pacheco A, Silva LF, Mesuret G, Boison D, Miras-Portugal MT, Letavic M, Artalejo AR, Bhattacharya A, Diaz-Hernandez M, et al. (2015) MicroRNA targeting of the P2X7 purinoceptor opposes a contralateral epileptogenic focus in the hippocampus. Sci Rep 5:17486
31. Jimenez-Pacheco A, Mesuret G, Sanz-Rodriguez A, Tanaka K, Mooney C, Conroy R, Miras-Portugal MT, Diaz-Hernandez M, Henshall DC, Engel T (2013) Increased neocortical expression of the P2X7 receptor after status epilepticus and anticonvulsant effect of P2X7 receptor antagonist A-438079. Epilepsia 54:1551-1561
32. Johnson MR, Behmoaras J, Bottolo L, Krishnan ML, Pernhorst K, Santoscoy PL, Rossetti T, Speed D, Srivastava PK, Chadeau-Hyam M, Hajji N, Dabrowska A, Rotival M, Razzaghi B, Kovac S, Wanisch K, Grillo FW, Sla-viero A, Langley SR, Shkura K, et al. (2015) Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epi-leptic hippocampus. Nat Commun 6:6031
33. Kim JE, Kang TC (2011) The P2X7 receptor-pannexin-1 complex decreases muscarinic acetylcholine receptor-mediated seizure susceptibility in mice. J Clin Invest 121:2037-2047
34. Klein S, Bankstahl M, Löscher W (2015) Interindividual variation in the effect of antiepileptic drugs in the intrahippocampal kainate model of mesial temporal lobe epilepsy in mice. Neuropharmacology 90:53-62
35. Kobow K, Auvin S, Jensen F, Löscher W, Mody I, Potschka H, Prince D, Sierra A, Simonato M, Pitkänen A, Nehlig A, Rho JM (2012) Finding a better drug for epilepsy: antiepileptogenesis targets. Epilepsia 53:1868-1876
36. Li T, Quan Lan J, Fredholm BB, Simon RP, Boison D (2007) Adenosine dysfunction in astrogliosis: cause for seizure generation? Neuron Glia Biol 3:353-366
37. Li T, Ren G, Lusardi T, Wilz A, Lan JQ, Iwasato T, Itohara S, Simon RP, Boison D (2008) Adenosine kinase is a target for the prediction and prevention of epileptogenesis in mice. J Clin Invest 118:571-582
38. Liu G, Gu B, He XP, Joshi RB, Wackerle HD, Rodriguiz RM, Wetsel WC, McNamara JO (2013) Transient inhibition of TrkB kinase after status epilepticus prevents development of temporal lobe epilepsy. Neuron 79: 31-38
39. Marchi N, Granata T, Janigro D (2014) Inflammatory pathways of seizure disorders. Trend Neurosci 37:55-65
40. Maroso M, Balosso S, Ravizza T, Iori V, Wright CI, French J, Vezzani A (2011) Interleukin-1beta biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice. Neurotherapeutics 8:304-315
41. Mesuret G, Engel T, Hessel EV, Sanz-Rodriguez A, Jimenez-Pacheco A, Miras-Portugal MT, Diaz-Hernandez M, Henshall DC (2014) P2X7 receptor inhibition interrupts the progression of seizures in immature rats and reduces hippocampal damage. CNS Neurosci Ther 20:556-564
42. Miras-Portugal MT, Díaz-Hernández M, Giráldez L, Hervás C, Gómez-Villafuertes R, Sen RP, Gualix J, Pintor J (2003) P2X7 receptors in rat brain: presence in synaptic terminals and granule cells. Neurochem Res 28:1597-1605
43. Monif M, Reid CA, Powell KL, Smart ML, Williams DA (2009) The P2X7 receptor drives microglial activation and proliferation: a trophic role for P2X7R pore. J Neurosci 29:3781-3791
44. Moshé SL, Perucca E, Ryvlin P, Tomson T (2015) Epilepsy: new advances. Lancet 385:884-898
45. Mouri G, Jimenez-Mateos E, Engel T, Dunleavy M, Hatazaki S, Paucard A, Matsushima S, Taki W, Henshall DC (2008) Unilateral hippocampal CA3-predominant damage and short latency epileptogenesis after intraamygdala microinjection of kainic acid in mice. Brain Res 1213:140-151
46. Murphy N, Cowley TR, Richardson JC, Virley D, Upton N, Walter D, Lynch MA (2012) The neuroprotective effect of a specific P2X(7) receptor antagonist derives from its ability to inhibit assembly of the NLRP3 inflammasome in glial cells. Brain Pathol 22:295-306
47. Narkilahti S, Nissinen J, Pitkänen A (2003) Administration of caspase 3 inhibitor during and after status epilepticus in rat: effect on neuronal damage and epileptogenesis. Neuropharmacology 44:1068-1088
48. Newson R (2006a) Confidence intervals for rank statistics: Somers’ D and extensions. Stata J 6:309-334.
49. Newson R (2006b) Confidence intervals for rank statistics: percentile slopes, differences, and ratios. Stata J 6:497-520.
50. Ortinski PI, Dong J, Mungenast A, Yue C, Takano H, Watson DJ, Haydon PG, Coulter DA (2010) Selective induction of astrocytic gliosis generates deficits in neuronal inhibition. Nat Neurosci 13:584-591
51. Pitkänen A, Lukasiuk K (2011) Mechanisms of epileptogenesis and poten-tial treatment targets. Lancet Neurol 10:173-186
52. Pusch M, Neher E (1988) Rates of diffusional exchange between small cells and a measuring patch pipette. Pflugers Arch 411:204-211
53. Rappold PM, Lynd-Balta E, Joseph SA (2006) P2X7 receptor immunoreac-tive profile confined to resting and activated microglia in the epileptic brain. Brain Res 1089:171-178
54. Riban V, Bouilleret V, Pham-Lê BT, Fritschy JM, Marescaux C, Depaulis A (2002) Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy. Neuroscience 112:101-111
55. Robel S, Buckingham SC, Boni JL, Campbell SL, Danbolt NC, Riedemann T, Sutor B, Sontheimer H (2015) Reactive astrogliosis causes the development of spontaneous seizures. J Neurosci 35:3330-3345
56. Roth TL, Nayak D, Atanasijevic T, Koretsky AP, Latour LL, McGavern DB (2014) Transcranial amelioration of inflammation and cell death after brain injury. Nature 505:223-228
57. Salter MW, Beggs S (2014) Sublime microglia: expanding roles for the guardians of the CNS. Cell 158:15-24
58. Sim JA, Young MT, Sung HY, North RA, Surprenant A (2004) Reanalysis of P2X7 receptor expression in rodent brain. J Neurosci 24:6307-6314
59. Soni N, Koushal P, Reddy BV, Deshmukh R, Kumar P (2015) Effect of GLT-1 modulator and P2X7 antagonists alone and in combination in the kindling model of epilepsy in rats. Epilepsy Behav 48:4-14
60. Sperlágh B, Illes P (2014) P2X7 receptor: an emerging target in central nervous system diseases. Trends Pharmacol Sci 35:537-547
61. Sperlágh B, Köfalvi A, Deuchars J, Atkinson L, Milligan CJ, Buckley NJ, Vizi ES (2002) Involvement of P2X7 receptors in the regulation of neurotransmitter release in the rat hippocampus. J Neurochem 81:1196-1211
62. Surprenant A, North RA (2009) Signaling at purinergic P2X receptors. Annu Rev Physiol 71:333-359
63. Vezzani A, Balosso S, Maroso M, Zardoni D, Noé F, Ravizza T (2010) ICE/ caspase 1 inhibitors and IL-1beta receptor antagonists as potential therapeutics in epilepsy. Curr Opin Investig Drugs 11:43-50
64. Vezzani A, French J, Bartfai T, Baram TZ (2011) The role of inflammation in epilepsy. Nat Rev Neurology 7:31-40
65. Vianna EP, Ferreira AT, Naffah-Mazzacoratti MG, Sanabria ER, Funke M, Cavalheiro EA, Fernandes MJ (2002) Evidence that ATP participates in the pathophysiology of pilocarpine-induced temporal lobe epilepsy: fluo-rimetric, immunohistochemical, and Western blot studies. Epilepsia 43 [Suppl 5]:227-229.
66. Viviani B, Bartesaghi S, Gardoni F, Vezzani A, Behrens MM, Bartfai T, Binaglia M, Corsini E, Di Luca M, Galli CL, Marinovich M (2003) Interleukin-1÷ enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci 23: 8692-8700
67. Wang X, Arcuino G, Takano T, Lin J, Peng WG, Wan P, Li P, Xu Q, Liu QS, Goldman SA, Nedergaard M (2004) P2X7 receptor inhibition improves recovery after spinal cord injury. Nat Med 10:821-827
68. Williams PA, White AM, Clark S, Ferraro DJ, Swiercz W, Staley KJ, Dudek FE (2009) Development of spontaneous recurrent seizures after kainate-induced status epilepticus. J Neurosci 29:2103-2112
69. Yu Y, Ugawa S, Ueda T, Ishida Y, Inoue K, Kyaw Nyunt A, Umemura A, Mase M, Yamada K, Shimada S (2008) Cellular localization of P2X7 receptor mRNA in the rat brain. Brain Res 1194:45-55
70. Zhou L, Qi X, Potashkin JA, Abdul-Karim FW, Gorodeski GI (2008) MicroRNAs miR-186 and miR-150 downregulate expression of the proapoptotic purinergic P2X7 receptor by activation of instability sites at the 3-untranslated region of the gene that decrease steady-state levels of the transcript. J Biol Chem 283:28274-28286