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Lipid Signaling in Experimental Epilepsy

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Abstract

Glutamate release activates signaling pathways important for learning and memory, and over-stimulation of these pathways during seizures leads to aberrant synaptic plasticity associated with hyper-excitable, seizure-prone states. Seizures induce rapid accumulation of membrane lipid-derived fatty acids at the synapses which, evidence suggests, regulate maladaptive connectivity. Here we give an overview of the significance of the arachidonyl- and inositol-derived messengers, prostaglandins (PGs) and diacylglycerol (DAG), in experimental models of epilepsy. We use studies conducted in our own laboratory to highlight the pro-epileptogenic role of cyclooxygenase-2 (COX-2) and its products, the PGs, and we discuss the possible mechanisms by which PGs may regulate membrane excitability and synaptic transmission at the cellular level. We conclude with a discussion of AA-DAG signaling in synaptic plasticity and seizure susceptibility with an emphasis on recent studies in our laboratory involving DAG kinase ε (DGKε)-knockout mice.

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References

  1. H. G. Minkwitz (1976) ArticleTitleDevelopment of neuronal structure in the hippocampus during pre- and post-natal ontogenesis in the albino rat. III. Morphometric determination of ontogenetic changes in dendrite structure and spine distribution on pyramidal neurons (CA1) of the hippocampus J. Hirnforsch. 17 255–275 Occurrence Handle1002983

    PubMed  Google Scholar 

  2. R. A. Altschuler (1979) ArticleTitleMorphometry of the effect of increased experience and training on synaptic density in area CA3 of the rat hippocampus J. Histochem. Cytochem. 27 1548–1550 Occurrence Handle512348

    PubMed  Google Scholar 

  3. M. B. Moser M. Trommald P. Andersen (1994) ArticleTitleAn increase in dendritic spine density on hippocampal CA1 pyramidal cells following spatial learning in adult rats suggests the formation of new synapses Proc. Natl. Acad. Sci. USA 91 12673–12675 Occurrence Handle7809099

    PubMed  Google Scholar 

  4. T. Arendt M. K. Bruckner V. Bigl L. Marcova (1995) ArticleTitleDendritic reorganisation in the basal forebrain under degenerative conditions and its defects in Alzheimer’s disease. II. Ageing, Korsakoff’s disease, Parkinson’s disease, and Alzheimer’s disease J. Comp. Neurol. 351 189–222 Occurrence Handle10.1002/cne.903510203 Occurrence Handle7535318

    Article  PubMed  Google Scholar 

  5. L. Ouda F. C. Nwabueze-Ogbo R. Druga J. Syka (2003) ArticleTitleNADPH-diaphorase-positive neurons in the auditory cortex of young and old rats Neuroreport 14 363–366 Occurrence Handle10.1097/00001756-200303030-00013 Occurrence Handle12634484

    Article  PubMed  Google Scholar 

  6. T. Harder (2003) ArticleTitleFormation of functional cell membrane domains: the interplay of lipid- and protein-mediated interactions Philos. Trans. R. Soc. Lond. B. Biol. Sci. 358 863–868 Occurrence Handle10.1098/rstb.2003.1274 Occurrence Handle12803918

    Article  PubMed  Google Scholar 

  7. J. W. Phillis M. H. O’Regan (2004) ArticleTitleA potentially critical role of phospholipases in central nervous system ischemic, traumatic, and neurodegenerative disorders Brain Res. Brain Res. Rev. 44 13–47 Occurrence Handle10.1016/j.brainresrev.2003.10.002 Occurrence Handle14739001

    Article  PubMed  Google Scholar 

  8. N. G. Bazan (2003) ArticleTitleSynaptic lipid signaling: Significance of polyunsaturated fatty acids and platelet-activating factor J. Lipid Res. 44 2221–2233 Occurrence Handle10.1194/jlr.R300013-JLR200 Occurrence Handle13130128

    Article  PubMed  Google Scholar 

  9. J. D. Clark L. L. Lin R. W. Kriz C. S. Ramesha L. A. Sultzman A. Y. Lin N. Milona J. L. Knopf (1991) ArticleTitleA novel arachidonic acid-selective cytosolic PLA2 contains a Ca (2+)-dependent translocation domain with homology to PKC and GAP Cell 65 1043–1051 Occurrence Handle10.1016/0092-8674(91)90556-E Occurrence Handle1904318

    Article  PubMed  Google Scholar 

  10. P. Nicotera G. Bellomo S. Orrenius (1992) ArticleTitleCalcium-mediated mechanisms in chemically induced cell death Annu. Rev. Pharmacol. Toxicol. 32 449–470 Occurrence Handle10.1146/annurev.pa.32.040192.002313 Occurrence Handle1605574

    Article  PubMed  Google Scholar 

  11. N. G. Bazan G. Allan E. B. Rodriguez Turco Particlede (1993) ArticleTitleRole of phospholipase A2 and membrane-derived lipid second messengers in membrane function and transcriptional activation of genes: implications in cerebral ischemia and neuronal excitability Prog. Brain Res. 96 247–257 Occurrence Handle8332745

    PubMed  Google Scholar 

  12. L. A. Horrocks A. A. Farooqui (1994) NMDA-receptor-stimulated release of arachidonic acid: Mechanisms for the Bazan effect A .M. Municio M.T. Miras-Portugal (Eds) Cell signal transduction, second messengers, and protein phosphorylation in health and disease Plenum Press New York 113–128

    Google Scholar 

  13. V. L. Marcheselli N. G. Bazan (1996) ArticleTitleSustained induction of prostaglandin endoperoxide synthase-2 by seizures in hippocampus. Inhibition by a platelet-activating factor antagonist J. Biol. Chem. 271 24794–24799 Occurrence Handle10.1074/jbc.271.40.24794 Occurrence Handle8798751

    Article  PubMed  Google Scholar 

  14. N. G. Bazan B. Tu E. B. Rodriguez de Turco (2002) ArticleTitleWhat synaptic lipid signaling tells us about seizure-induced damage and epileptogenesis Prog. Brain Res. 135 175–185 Occurrence Handle12143339

    PubMed  Google Scholar 

  15. W. L. Smith L. J. Marnett (1991) ArticleTitleProstaglandin endoperoxide synthase: structure and catalysis Biochim. Biophys. Acta 1083 1–17 Occurrence Handle1903304

    PubMed  Google Scholar 

  16. S. Thoren R. Weinander S. Saha C. Jegerschold P. L. Pettersson B. Samuelsson H. Hebert M. Hamberg R. Morgenstern P. J. Jakobsson (2003) ArticleTitleHuman microsomal prostaglandin E synthase-1: Purification, functional characterization, and projection structure determination J. Biol. Chem. 278 22199–22209 Occurrence Handle10.1074/jbc.M303227200 Occurrence Handle12672824

    Article  PubMed  Google Scholar 

  17. K. Seibert Y. Zhang K. Leahy S. Hauser J. Masferrer W. Perkins L. Lee P. Isakson (1994) ArticleTitlePharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain Proc. Natl. Acad. Sci. USA 91 12013–12017 Occurrence Handle7991575

    PubMed  Google Scholar 

  18. M. Nakayama K. Uchimura R. L. Zhu T. Nagayama M. E. Rose R. A. Stetler P. C. Isakson J. Chen S. H. Graham (1998) ArticleTitleCyclooxygenase-2 inhibition prevents delayed death of CA1 hippocampal neurons following global ischemia Proc. Natl. Acad. Sci. USA 95 10954–10959 Occurrence Handle10.1073/pnas.95.18.10954 Occurrence Handle9724811

    Article  PubMed  Google Scholar 

  19. A. V. Ershov N. G. Bazan (1999) ArticleTitleInduction of cyclooxygenase-2 gene expression in retinal pigment epithelium cells by photoreceptor rod outer segment phagocytosis and growth factors J. Neurosci. Res. 58 254–261 Occurrence Handle10.1002/(SICI)1097-4547(19991015)58:2<254::AID-JNR5>3.0.CO;2-U Occurrence Handle10502281

    Article  PubMed  Google Scholar 

  20. C. Hoffmann (2000) ArticleTitleCOX-2 in brain and spinal cord implications for therapeutic use Curr. Med. Chem. 7 1113–1120 Occurrence Handle11032961

    PubMed  Google Scholar 

  21. W. E. Kaufmann P. F. Worley J. Pegg M. Bremer P. Isakson (1996) ArticleTitleCOX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex Proc. Natl. Acad. Sci. USA 93 2317–2321 Occurrence Handle10.1073/pnas.93.6.2317 Occurrence Handle8637870

    Article  PubMed  Google Scholar 

  22. N. G. Bazan (1995) ArticleTitleInflammation. A signal terminator Nature 374 501–502 Occurrence Handle10.1038/374501a0 Occurrence Handle7700374

    Article  PubMed  Google Scholar 

  23. N. G. Bazan M. G. Packard L. Teather G. Allan (1997) ArticleTitleBioactive lipids in excitatory neurotransmission and neuronal plasticity Neurochem. Int. 30 225–231 Occurrence Handle10.1016/S0197-0186(96)00020-4 Occurrence Handle9017670

    Article  PubMed  Google Scholar 

  24. G. V. Goddard D. C. McIntyre C. K. Leech (1969) ArticleTitleA permanent change in brain function resulting from daily electrical stimulation Exp. Neurol. 25 295–330 Occurrence Handle10.1016/0014-4886(69)90128-9 Occurrence Handle4981856

    Article  PubMed  Google Scholar 

  25. B. Tu N. G. Bazan (2003) ArticleTitleHippocampal kindling epileptogenesis upregulates neuronal cyclooxygenase-2 expression in neocortex Exp. Neurol. 179 167–175 Occurrence Handle10.1016/S0014-4886(02)00019-5 Occurrence Handle12618123

    Article  PubMed  Google Scholar 

  26. C. W. Leffler D. W. Busija (1985) ArticleTitleArachidonate metabolism on the cerebral surface of newborn pigs Prostaglandins 30 811–817 Occurrence Handle10.1016/0090-6980(85)90009-7 Occurrence Handle3936120

    Article  PubMed  Google Scholar 

  27. C. Chen N. G. Bazan (2005) ArticleTitleEndogenous PGE2 regulates membrane excitability and synaptic transmission in hippocampal CA1 pyramidal neurons J. Neurophysiol. 93 929–941 Occurrence Handle10.1152/jn.00696.2004 Occurrence Handle15653788

    Article  PubMed  Google Scholar 

  28. A. N. Hata R. M. Breyer (2004) ArticleTitlePharmacology and signaling of prostaglandin receptors: Multiple roles in inflammation and immune modulation Pharmacol. Ther. 103 147–166 Occurrence Handle10.1016/j.pharmthera.2004.06.003 Occurrence Handle15369681

    Article  PubMed  Google Scholar 

  29. M. N. Hodgkin T. R. Pettitt A. Martin R. H. Michell A. J. Pemberton M. J. Wakelam (1998) ArticleTitleDiacylglycerols and phosphatidates: which molecular species are intracellular messengers? Trends Biochem. Sci. 23 200–204 Occurrence Handle10.1016/S0968-0004(98)01200-6 Occurrence Handle9644971

    Article  PubMed  Google Scholar 

  30. M. I. Aveldano N. G. Bazan (1975) ArticleTitleRapid production of diacylglycerols enriched in arachidonate and stearate during early brain ischemia J. Neurochem. 25 919–920 Occurrence Handle1206411

    PubMed  Google Scholar 

  31. M. I. Aveldano Caldironi Particlede N. G. Bazan (1979) ArticleTitleAlpha-Methyl-p-tyrosine inhibits the production of free arachidonic acid and diacylglycerols in brain after a single electroconvulsive shock Neurochem. Res. 4 213–221 Occurrence Handle10.1007/BF00964145 Occurrence Handle460521

    Article  PubMed  Google Scholar 

  32. G. Y. Sun J. Xu M. D. Jensen A. Simonyi (2004) ArticleTitlePhospholipase A2 in the central nervous system: Implications for neurodegenerative diseases J. Lipid Res. 45 205–213 Occurrence Handle10.1194/jlr.R300016-JLR200 Occurrence Handle14657205

    Article  PubMed  Google Scholar 

  33. Y. Nishizuka (1995) ArticleTitleProtein kinase C and lipid signaling for sustained cellular responses FASEB J. 9 484–496 Occurrence Handle7737456

    PubMed  Google Scholar 

  34. N. Brose C. Rosenmund (2002) ArticleTitleMove over protein kinase C, you’ve got company: Alternative cellular effectors of diacylglycerol and phorbol esters J. Cell Sci. 115 4399–4411

    Google Scholar 

  35. T. R. Pettitt M. J. Wakelam (1999) ArticleTitleDiacylglycerol kinase epsilon, but not zeta, selectively removes polyunsaturated diacylglycerol, inducing altered protein kinase C distribution in vivo J. Biol. Chem. 274 36181–36186 Occurrence Handle10.1074/jbc.274.51.36181 Occurrence Handle10593903

    Article  PubMed  Google Scholar 

  36. A. Abeliovich C. Chen Y. Goda A. J. Silva C. F. Stevens S. Tonegawa (1993) ArticleTitleModified hippocampal long-term potentiation in PKC gamma-mutant mice Cell 75 1253–1262 Occurrence Handle10.1016/0092-8674(93)90613-U Occurrence Handle8269509

    Article  PubMed  Google Scholar 

  37. A. Abeliovich R. Paylor C. Chen J. J. Kim J. M. Wehner S. Tonegawa (1993) ArticleTitlePKC gamma mutant mice exhibit mild deficits in spatial and contextual learning Cell 75 1263–1271 Occurrence Handle10.1016/0092-8674(93)90614-V Occurrence Handle8269510

    Article  PubMed  Google Scholar 

  38. A. Aiba M. Kano C. Chen M. E. Stanton G. D. Fox K. Herrup T. A. Zwingman S. Tonegawa (1994) ArticleTitleDeficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice Cell 79 377–388 Occurrence Handle10.1016/0092-8674(94)90204-6 Occurrence Handle7954803

    Article  PubMed  Google Scholar 

  39. F. Conquet Z. I. Bashir C. H. Davies H. Daniel F. Ferraguti F. Bordi K. Franz-Bacon A. Reggiani V. Matarese F. Conde (1994) ArticleTitleMotor deficit and impairment of synaptic plasticity in mice lacking mGluR1 Nature 372 237–243 Occurrence Handle10.1038/372237a0 Occurrence Handle7969468

    Article  PubMed  Google Scholar 

  40. S. Nakanishi (1994) ArticleTitleMetabotropic glutamate receptors: Synaptic transmission, modulation, and plasticity Neuron 13 1031–1037 Occurrence Handle10.1016/0896-6273(94)90043-4 Occurrence Handle7946343

    Article  PubMed  Google Scholar 

  41. V. W. Wilsch T. Behnisch T. Jager K. G. Reymann D. Balschun (1998) ArticleTitleWhen are class I metabotropic glutamate receptors necessary for long-term potentiation? J. Neurosci. 18 6071–6080 Occurrence Handle9698302

    PubMed  Google Scholar 

  42. F. Bordi A. Ugolini (1999) ArticleTitleGroup I metabotropic glutamate receptors: implications for brain diseases Prog. Neurobiol. 59 55–79 Occurrence Handle10.1016/S0301-0082(98)00095-1 Occurrence Handle10416961

    Article  PubMed  Google Scholar 

  43. R. S. Petralia Y. X. Wang S. Singh C. Wu L. Shi J. Wei R. J. Wenthold (1997) ArticleTitleA monoclonal antibody shows discrete cellular and subcellular localizations of mGluR1 alpha␣metabotropic glutamate receptors J. Chem. Neuroanat. 13 77–93 Occurrence Handle10.1016/S0891-0618(97)00023-9 Occurrence Handle9285353

    Article  PubMed  Google Scholar 

  44. A. Berthele D. J. Laurie S. Platzer W. Zieglgansberger T. R. Tolle B. Sommer (1998) ArticleTitleDifferential expression of rat and human type I metabotropic glutamate receptor splice variant messenger RNAs Neuroscience 85 733–749 Occurrence Handle10.1016/S0306-4522(97)00670-2 Occurrence Handle9639268

    Article  PubMed  Google Scholar 

  45. E. B. Rodriguez Turco Particlede W. Tang M. K. Topham F. Sakane V. L. Marcheselli C. Chen A. Taketomi S. M. Prescott N. G. Bazan (2001) ArticleTitleDiacylglycerol kinase epsilon regulates seizure susceptibility and long-term potentiation through arachidonoyl-inositol lipid signaling Proc. Natl. Acad. Sci. USA 98 4740–4745 Occurrence Handle10.1073/pnas.081536298 Occurrence Handle11287665

    Article  PubMed  Google Scholar 

  46. S. M. Prescott P. W. Majerus (1981) ArticleTitleThe fatty acid composition of phosphatidylinositol from thrombin-stimulated human platelets J. Biol. Chem. 256 579–582 Occurrence Handle7451460

    PubMed  Google Scholar 

  47. N. G. Bazan E. B. Rodriguez Turco Particlede G. Allan (1995) ArticleTitleMediators of injury in neurotrauma: Intracellular signal transduction and gene expression J. Neurotrauma 12 791–814 Occurrence Handle8594208

    PubMed  Google Scholar 

  48. E. M. Ullian K. S. Christopherson B. A. Barres (2004) ArticleTitleRole for glia in synaptogenesis Glia 47 209–216 Occurrence Handle10.1002/glia.20082 Occurrence Handle15252809

    Article  PubMed  Google Scholar 

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  1. LSU Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, 70112, LA, USA

    Kasie K. Cole-Edwards & Nicolas G. Bazan

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  2. Nicolas G. Bazan
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Cole-Edwards, K.K., Bazan, N.G. Lipid Signaling in Experimental Epilepsy. Neurochem Res 30, 847–853 (2005). https://doi.org/10.1007/s11064-005-6878-4

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