Neuronal and glial DNA methylation and gene expression changes in early epileptogenesis


Autoři: Toni C. Berger aff001;  Magnus D. Vigeland aff003;  Hanne S. Hjorthaug aff003;  Lars Etholm aff004;  Cecilie G. Nome aff002;  Erik Taubøll aff001;  Kjell Heuser aff001;  Kaja K. Selmer aff003
Působiště autorů: Department of Neurology, Oslo University Hospital, Oslo, Norway aff001;  University of Oslo, Oslo, Norway aff002;  Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway aff003;  National Center for Epilepsy, Oslo University Hospital, Sandvika, Norway aff004;  Department of Neurology, Section for Neurophysiology, Oslo University Hospital, Oslo, Norway aff005;  Division of Clinical Neuroscience, Department of Research and Development, Oslo University Hospital, Oslo, Norway aff006
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226575

Souhrn

Background and aims

Mesial Temporal Lobe Epilepsy is characterized by progressive changes of both neurons and glia, also referred to as epileptogenesis. No curative treatment options, apart from surgery, are available. DNA methylation (DNAm) is a potential upstream mechanism in epileptogenesis and may serve as a novel therapeutic target. To our knowledge, this is the first study to investigate epilepsy-related DNAm, gene expression (GE) and their relationship, in neurons and glia.

Methods

We used the intracortical kainic acid injection model to elicit status epilepticus. At 24 hours post injection, hippocampi from eight kainic acid- (KA) and eight saline-injected (SH) mice were extracted and shock frozen. Separation into neurons and glial nuclei was performed by flow cytometry. Changes in DNAm and gene expression were measured with reduced representation bisulfite sequencing (RRBS) and mRNA-sequencing (mRNAseq). Statistical analyses were performed in R with the edgeR package.

Results

We observed fulminant DNAm- and GE changes in both neurons and glia at 24 hours after initiation of status epilepticus. The vast majority of these changes were specific for either neurons or glia. At several epilepsy-related genes, like HDAC11, SPP1, GAL, DRD1 and SV2C, significant differential methylation and differential gene expression coincided.

Conclusion

We found neuron- and glia-specific changes in DNAm and gene expression in early epileptogenesis. We detected single genetic loci in several epilepsy-related genes, where DNAm and GE changes coincide, worth further investigation. Further, our results may serve as an information source for neuronal and glial alterations in both DNAm and GE in early epileptogenesis.

Klíčová slova:

DNA methylation – Gene expression – Immune receptor signaling – Immune receptors – Neurons – Protein domains – Cytokine receptors – Transmembrane receptors


Zdroje

1. Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005;46(4):470–2. doi: 10.1111/j.0013-9580.2005.66104.x 15816939

2. Ngugi AK, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Estimation of the burden of active and life-time epilepsy: A meta-analytic approach. Epilepsia. 2010;51(5):883–90. doi: 10.1111/j.1528-1167.2009.02481.x 20067507

3. Semah F, Picot MC, Adam C, Broglin D, Arzimanoglou A, Bazin B, et al. Is the underlying cause of epilepsy a major prognostic factor for recurrence? Neurology. 1998;51(5):1256–62. doi: 10.1212/wnl.51.5.1256 9818842

4. de Lanerolle NC, Kim JH, Williamson A, Spencer SS, Zaveri HP, Eid T, et al. A retrospective analysis of hippocampal pathology in human temporal lobe epilepsy: evidence for distinctive patient subcategories. Epilepsia. 2003;44(5):677–87. doi: 10.1046/j.1528-1157.2003.32701.x 12752467

5. Blumcke I, Thom M, Aronica E, Armstrong DD, Bartolomei F, Bernasconi A, et al. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a Task Force report from the ILAE Commission on Diagnostic Methods. Epilepsia. 2013;54(7):1315–29. doi: 10.1111/epi.12220 23692496

6. Wieser HG. ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsia. 2004;45(6):695–714. doi: 10.1111/j.0013-9580.2004.09004.x 15144438

7. Pitkanen A, Lukasiuk K. Molecular and cellular basis of epileptogenesis in symptomatic epilepsy. Epilepsy & behavior: E&B. 2009;14 Suppl 1:16–25.

8. Pitkanen A, Engel J Jr. Past and present definitions of epileptogenesis and its biomarkers. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics. 2014;11(2):231–41.

9. Patel DC, Tewari BP, Chaunsali L, Sontheimer H. Neuron–glia interactions in the pathophysiology of epilepsy. Nature Reviews Neuroscience. 2019;20(5):282–97. doi: 10.1038/s41583-019-0126-4 30792501

10. Mathern GW, Babb TL, Vickrey BG, Melendez M, Pretorius JK. The clinical-pathogenic mechanisms of hippocampal neuron loss and surgical outcomes in temporal lobe epilepsy. Brain: a journal of neurology. 1995;118 (Pt 1):105–18.

11. Houser CR. Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy. Brain research. 1990;535(2):195–204. doi: 10.1016/0006-8993(90)91601-c 1705855

12. Houser C, Miyashiro J, Swartz B, Walsh G, Rich J, Delgado-Escueta A. Altered patterns of dynorphin immunoreactivity suggest mossy fiber reorganization in human hippocampal epilepsy. The Journal of Neuroscience. 1990;10(1):267–82. doi: 10.1523/JNEUROSCI.10-01-00267.1990 1688934

13. de Lanerolle NC, Kim JH, Robbins RJ, Spencer DD. Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy. Brain research. 1989;495(2):387–95. doi: 10.1016/0006-8993(89)90234-5 2569920

14. Tauck DL, Nadler JV. Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats. The Journal of neuroscience: the official journal of the Society for Neuroscience. 1985;5(4):1016–22.

15. Bedner P, Dupper A, Huttmann K, Muller J, Herde MK, Dublin P, et al. Astrocyte uncoupling as a cause of human temporal lobe epilepsy. Brain: a journal of neurology. 2015;138(Pt 5):1208–22.

16. Vezzani A, Granata T. Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia. 2005;46(11):1724–43. doi: 10.1111/j.1528-1167.2005.00298.x 16302852

17. Rigau V, Morin M, Rousset MC, de Bock F, Lebrun A, Coubes P, et al. Angiogenesis is associated with blood-brain barrier permeability in temporal lobe epilepsy. Brain: a journal of neurology. 2007;130(Pt 7):1942–56.

18. Seifert G, Steinhäuser C. Neuron–astrocyte signaling and epilepsy. Experimental Neurology. 2013;244:4–10. doi: 10.1016/j.expneurol.2011.08.024 21925173

19. Loscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia. 2011;52(4):657–78. doi: 10.1111/j.1528-1167.2011.03024.x 21426333

20. Pitkanen A, Lukasiuk K. Mechanisms of epileptogenesis and potential treatment targets. The Lancet Neurology. 2011;10(2):173–86. doi: 10.1016/S1474-4422(10)70310-0 21256455

21. Loscher W, Klitgaard H, Twyman RE, Schmidt D. New avenues for anti-epileptic drug discovery and development. Nature reviews Drug discovery. 2013;12(10):757–76. doi: 10.1038/nrd4126 24052047

22. Luo C, Hajkova P, Ecker JR. Dynamic DNA methylation: In the right place at the right time. Science (New York, NY). 2018;361(6409):1336–40.

23. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, et al. Global epigenomic reconfiguration during mammalian brain development. Science (New York, NY). 2013;341(6146):1237905.

24. Sanosaka T, Imamura T, Hamazaki N, Chai M, Igarashi K, Ideta-Otsuka M, et al. DNA Methylome Analysis Identifies Transcription Factor-Based Epigenomic Signatures of Multilineage Competence in Neural Stem/Progenitor Cells. Cell reports. 2017;20(12):2992–3003. doi: 10.1016/j.celrep.2017.08.086 28930691

25. Smith ZD, Meissner A. DNA methylation: roles in mammalian development. Nature reviews Genetics. 2013;14(3):204–20. doi: 10.1038/nrg3354 23400093

26. Guo JU, Ma DK, Mo H, Ball MP, Jang MH, Bonaguidi MA, et al. Neuronal activity modifies the DNA methylation landscape in the adult brain. Nature neuroscience. 2011;14(10):1345–51. doi: 10.1038/nn.2900 21874013

27. Zhu Q, Wang L, Zhang Y, Zhao FH, Luo J, Xiao Z, et al. Increased expression of DNA methyltransferase 1 and 3a in human temporal lobe epilepsy. Journal of molecular neuroscience: MN. 2012;46(2):420–6. doi: 10.1007/s12031-011-9602-7 21826395

28. Williams-Karnesky RL, Sandau US, Lusardi TA, Lytle NK, Farrell JM, Pritchard EM, et al. Epigenetic changes induced by adenosine augmentation therapy prevent epileptogenesis. The Journal of clinical investigation. 2013;123(8):3552–63. doi: 10.1172/JCI65636 23863710

29. Debski KJ, Pitkanen A, Puhakka N, Bot AM, Khurana I, Harikrishnan KN, et al. Etiology matters—Genomic DNA Methylation Patterns in Three Rat Models of Acquired Epilepsy. Scientific reports. 2016;6:25668. doi: 10.1038/srep25668 27157830

30. Ryley Parrish R, Albertson AJ, Buckingham SC, Hablitz JJ, Mascia KL, Davis Haselden W, et al. Status epilepticus triggers early and late alterations in brain-derived neurotrophic factor and NMDA glutamate receptor Grin2b DNA methylation levels in the hippocampus. Neuroscience. 2013;248:602–19. doi: 10.1016/j.neuroscience.2013.06.029 23811393

31. Xie N, Zhou Y, Sun Q, Tang B. Novel Epigenetic Techniques Provided by the CRISPR/Cas9 System. Stem Cells International. 2018;2018:7834175. doi: 10.1155/2018/7834175 30123293

32. Liu XS, Wu H, Ji X, Stelzer Y, Wu X, Czauderna S, et al. Editing DNA Methylation in the Mammalian Genome. Cell. 2016;167(1):233–47.e17. doi: 10.1016/j.cell.2016.08.056 27662091

33. Nomura W. Development of Toolboxes for Precision Genome/Epigenome Editing and Imaging of Epigenetics. Chemical record (New York, NY). 2018;18(12):1717–26.

34. Kozlenkov A, Roussos P, Timashpolsky A, Barbu M, Rudchenko S, Bibikova M, et al. Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites. Nucleic Acids Research. 2014;42(1):109–27. doi: 10.1093/nar/gkt838 24057217

35. Iwamoto K, Bundo M, Ueda J, Oldham MC, Ukai W, Hashimoto E, et al. Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons. Genome research. 2011;21(5):688–96. doi: 10.1101/gr.112755.110 21467265

36. Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2008;28(1):264–78.

37. Doyle JP, Dougherty JD, Heiman M, Schmidt EF, Stevens TR, Ma G, et al. Application of a translational profiling approach for the comparative analysis of CNS cell types. Cell. 2008;135(4):749–62. doi: 10.1016/j.cell.2008.10.029 19013282

38. Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG, et al. Genomic analysis of reactive astrogliosis. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2012;32(18):6391–410.

39. Gasparoni G, Bultmann S, Lutsik P, Kraus TFJ, Sordon S, Vlcek J, et al. DNA methylation analysis on purified neurons and glia dissects age and Alzheimer's disease-specific changes in the human cortex. Epigenetics & chromatin. 2018;11(1):41–.

40. Kozlenkov A, Jaffe AE, Timashpolsky A, Apontes P, Rudchenko S, Barbu M, et al. DNA Methylation Profiling of Human Prefrontal Cortex Neurons in Heroin Users Shows Significant Difference between Genomic Contexts of Hyper- and Hypomethylation and a Younger Epigenetic Age. Genes. 2017;8(6):152.

41. Rizzardi LF, Hickey PF, Rodriguez DiBlasi V, Tryggvadóttir R, Callahan CM, Idrizi A, et al. Neuronal brain-region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability. Nature neuroscience. 2019;22(2):307–16. doi: 10.1038/s41593-018-0297-8 30643296

42. Jiang Y, Matevossian A, Huang H-S, Straubhaar J, Akbarian S. Isolation of neuronal chromatin from brain tissue. BMC neuroscience. 2008;9:42–. doi: 10.1186/1471-2202-9-42 18442397

43. Boyle P, Clement K, Gu H, Smith ZD, Ziller M, Fostel JL, et al. Gel-free multiplexed reduced representation bisulfite sequencing for large-scale DNA methylation profiling. Genome Biology. 2012;13(10):R92. doi: 10.1186/gb-2012-13-10-r92 23034176

44. Cavalcante RG, Sartor MA. annotatr: genomic regions in context. Bioinformatics. 2017;33(15):2381–3. doi: 10.1093/bioinformatics/btx183 28369316

45. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26(1):139–40. doi: 10.1093/bioinformatics/btp616 19910308

46. Chen Y, Pal B, Visvader JE, Smyth GK. Differential methylation analysis of reduced representation bisulfite sequencing experiments using edgeR. F1000Research. 2017;6.

47. Wickham H. ggplot2: elegant graphics for data analysis: Springer; 2016.

48. Mederos S, Gonzalez-Arias C, Perea G. Astrocyte-Neuron Networks: A Multilane Highway of Signaling for Homeostatic Brain Function. Frontiers in synaptic neuroscience. 2018;10:45. doi: 10.3389/fnsyn.2018.00045 30542276

49. Herculano-Houzel S. The glia/neuron ratio: how it varies uniformly across brain structures and species and what that means for brain physiology and evolution. Glia. 2014;62(9):1377–91. doi: 10.1002/glia.22683 24807023

50. Zeisel A, Munoz-Manchado AB, Codeluppi S, Lonnerberg P, La Manno G, Jureus A, et al. Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science (New York, NY). 2015;347(6226):1138–42.

51. Mullen RJ, Buck CR, Smith AM. NeuN, a neuronal specific nuclear protein in vertebrates. Development (Cambridge, England). 1992;116(1):201–11.

52. Miller-Delaney SF, Das S, Sano T, Jimenez-Mateos EM, Bryan K, Buckley PG, et al. Differential DNA methylation patterns define status epilepticus and epileptic tolerance. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2012;32(5):1577–88.

53. Kobow K, Kaspi A, Harikrishnan KN, Kiese K, Ziemann M, Khurana I, et al. Deep sequencing reveals increased DNA methylation in chronic rat epilepsy. Acta neuropathologica. 2013;126(5):741–56. doi: 10.1007/s00401-013-1168-8 24005891

54. Miller-Delaney SFC, Bryan K, Das S, McKiernan RC, Bray IM, Reynolds JP, et al. Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy. Brain: a journal of neurology. 2015;138(3):616–31.

55. Long HY, Feng L, Kang J, Luo ZH, Xiao WB, Long LL, et al. Blood DNA methylation pattern is altered in mesial temporal lobe epilepsy. Scientific reports. 2017;7:43810. doi: 10.1038/srep43810 28276448

56. Lukasiuk K, Dabrowski M, Adach A, Pitkanen A. Epileptogenesis-related genes revisited. Progress in brain research. 2006;158:223–41. doi: 10.1016/S0079-6123(06)58011-2 17027699

57. Liu X, Ou S, Xu T, Liu S, Yuan J, Huang H, et al. New differentially expressed genes and differential DNA methylation underlying refractory epilepsy. Oncotarget. 2016;7(52):87402–16. doi: 10.18632/oncotarget.13642 27903967

58. Griffin NG, Wang Y, Hulette CM, Halvorsen M, Cronin KD, Walley NM, et al. Differential gene expression in dentate granule cells in mesial temporal lobe epilepsy with and without hippocampal sclerosis. Epilepsia. 2016;57(3):376–85. doi: 10.1111/epi.13305 26799155

59. Aronica E, Ravizza T, Zurolo E, Vezzani A. Astrocyte immune responses in epilepsy. Glia. 2012;60(8):1258–68. doi: 10.1002/glia.22312 22331574

60. Binder DK, Nagelhus EA, Ottersen OP. Aquaporin-4 and epilepsy. Glia. 2012;60(8):1203–14. doi: 10.1002/glia.22317 22378467

61. Boison D. Adenosine dysfunction in epilepsy. Glia. 2012;60(8):1234–43. doi: 10.1002/glia.22285 22700220

62. Carmignoto G, Haydon PG. Astrocyte calcium signaling and epilepsy. Glia. 2012;60(8):1227–33. doi: 10.1002/glia.22318 22389222

63. Coulter DA, Eid T. Astrocytic regulation of glutamate homeostasis in epilepsy. Glia. 2012;60(8):1215–26. doi: 10.1002/glia.22341 22592998

64. Heinemann U, Kaufer D, Friedman A. Blood-brain barrier dysfunction, TGFβ signaling, and astrocyte dysfunction in epilepsy. Glia. 2012;60(8):1251–7. doi: 10.1002/glia.22311 22378298

65. Steinhäuser C, Boison D. Epilepsy: crucial role for astrocytes. Glia. 2012;60(8):1191–. doi: 10.1002/glia.22300 22696194

66. Steinhäuser C, Seifert G, Bedner P. Astrocyte dysfunction in temporal lobe epilepsy: K+ channels and gap junction coupling. Glia. 2012;60(8):1192–202. doi: 10.1002/glia.22313 22328245

67. Takekawa M, Saito H. A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK. Cell. 1998;95(4):521–30. doi: 10.1016/s0092-8674(00)81619-0 9827804

68. Zhu RL, Graham SH, Jin K, Stetler RA, Simon RP, Chen J. Kainate induces the expression of the DNA damage-inducible gene, GADD45, in the rat brain. Neuroscience. 1997;81(3):707–20. doi: 10.1016/s0306-4522(97)00205-4 9316023

69. Ma DK, Jang M-H, Guo JU, Kitabatake Y, Chang M-L, Pow-Anpongkul N, et al. Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science (New York, NY). 2009;323(5917):1074–7.

70. Bryan L, Kordula T, Spiegel S, Milstien S. Regulation and functions of sphingosine kinases in the brain. Biochimica et biophysica acta. 2008;1781(9):459–66. doi: 10.1016/j.bbalip.2008.04.008 18485923

71. Karunakaran I, van Echten-Deckert G. Sphingosine 1-phosphate–A double edged sword in the brain. Biochimica et Biophysica Acta (BBA)—Biomembranes. 2017;1859(9, Part B):1573–82.

72. Fu P, Ebenezer DL, Ha AW, Suryadevara V, Harijith A, Natarajan V. Nuclear lipid mediators: Role of nuclear sphingolipids and sphingosine-1-phosphate signaling in epigenetic regulation of inflammation and gene expression. Journal of cellular biochemistry. 2018;119(8):6337–53. doi: 10.1002/jcb.26707 29377310

73. Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G, et al. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nature reviews Drug discovery. 2010;9(11):883–97. doi: 10.1038/nrd3248 21031003

74. Rothhammer V, Kenison JE, Tjon E, Takenaka MC, de Lima KA, Borucki DM, et al. Sphingosine 1-phosphate receptor modulation suppresses pathogenic astrocyte activation and chronic progressive CNS inflammation. Proc Natl Acad Sci U S A. 2017;114(8):2012–7. doi: 10.1073/pnas.1615413114 28167760

75. Das A, Arifuzzaman S, Kim SH, Lee YS, Jung KH, Chai YG. FTY720 (fingolimod) regulates key target genes essential for inflammation in microglial cells as defined by high-resolution mRNA sequencing. Neuropharmacology. 2017;119:1–14. doi: 10.1016/j.neuropharm.2017.03.034 28373076

76. Pitsch J, Kuehn JC, Gnatkovsky V, Muller JA, van Loo KMJ, de Curtis M, et al. Anti-epileptogenic and Anti-convulsive Effects of Fingolimod in Experimental Temporal Lobe Epilepsy. Molecular neurobiology. 2018.

77. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocrine reviews. 2001;22(2):153–83. doi: 10.1210/edrv.22.2.0428 11294822

78. Retamal MA, Froger N, Palacios-Prado N, Ezan P, Sáez PJ, Sáez JC, et al. Cx43 Hemichannels and Gap Junction Channels in Astrocytes Are Regulated Oppositely by Proinflammatory Cytokines Released from Activated Microglia. The Journal of Neuroscience. 2007;27(50):13781–92. doi: 10.1523/JNEUROSCI.2042-07.2007 18077690

79. Nimlamool W, Andrews RM, Falk MM. Connexin43 phosphorylation by PKC and MAPK signals VEGF-mediated gap junction internalization. Molecular biology of the cell. 2015;26(15):2755–68. doi: 10.1091/mbc.E14-06-1105 26063728

80. Laird DW. Connexin phosphorylation as a regulatory event linked to gap junction internalization and degradation. Biochimica et Biophysica Acta (BBA)—Biomembranes. 2005;1711(2):172–82.

81. Carmignoto G, Haydon PG. Astrocyte calcium signaling and epilepsy. Glia. 2012;60(8):1227–33. doi: 10.1002/glia.22318 22389222

82. Szokol K, Heuser K, Tang W, Jensen V, Enger R, Bedner P, et al. Augmentation of Ca(2+) signaling in astrocytic endfeet in the latent phase of temporal lobe epilepsy. Frontiers in cellular neuroscience. 2015;9:49–. doi: 10.3389/fncel.2015.00049 25762896

83. Heuser K, Eid T, Lauritzen F, Thoren AE, Vindedal GF, Taubøll E, et al. Loss of perivascular Kir4.1 potassium channels in the sclerotic hippocampus of patients with mesial temporal lobe epilepsy. Journal of neuropathology and experimental neurology. 2012;71(9):814–25. doi: 10.1097/NEN.0b013e318267b5af 22878665

84. Binder DK, Steinhäuser C. Functional changes in astroglial cells in epilepsy. Glia. 2006;54(5):358–68. doi: 10.1002/glia.20394 16886201

85. Irvine RF, Schell MJ. Back in the water: the return of the inositol phosphates. Nature reviews Molecular cell biology. 2001;2(5):327–38. doi: 10.1038/35073015 11331907

86. Chung S, Kim IH, Lee D, Park K, Kim JY, Lee YK, et al. The role of inositol 1,4,5-trisphosphate 3-kinase A in regulating emotional behavior and amygdala function. Scientific reports. 2016;6:23757. doi: 10.1038/srep23757 27053114

87. Kelley GG, Kaproth-Joslin KA, Reks SE, Smrcka AV, Wojcikiewicz RJH. G-protein-coupled receptor agonists activate endogenous phospholipase Cepsilon and phospholipase Cbeta3 in a temporally distinct manner. J Biol Chem. 2006;281(5):2639–48. doi: 10.1074/jbc.M507681200 16314422

88. Moss FJ, Viard P, Davies A, Bertaso F, Page KM, Graham A, et al. The novel product of a five-exon stargazin-related gene abolishes Ca(V)2.2 calcium channel expression. The EMBO journal. 2002;21(7):1514–23. doi: 10.1093/emboj/21.7.1514 11927536

89. Machnes ZM, Huang TC, Chang PK, Gill R, Reist N, Dezsi G, et al. DNA methylation mediates persistent epileptiform activity in vitro and in vivo. PloS one. 2013;8(10):e76299. doi: 10.1371/journal.pone.0076299 24098468

90. Chen X, Peng X, Wang L, Fu X, Zhou JX, Zhu B, et al. Association of RASgrf1 methylation with epileptic seizures. Oncotarget. 2017;8(28):46286–97. doi: 10.18632/oncotarget.18000 28611277

91. Riew T-R, Kim HL, Jin X, Choi J-H, Shin Y-J, Kim JS, et al. Spatiotemporal expression of osteopontin in the striatum of rats subjected to the mitochondrial toxin 3-nitropropionic acid correlates with microcalcification. Scientific reports. 2017;7:45173. doi: 10.1038/srep45173 28345671

92. Dianzani C, Bellavista E, Liepe J, Verderio C, Martucci M, Santoro A, et al. Extracellular proteasome-osteopontin circuit regulates cell migration with implications in multiple sclerosis. Scientific reports. 2017;7:43718–. doi: 10.1038/srep43718 28276434

93. Borges K, Gearing M, Rittling S, Sorensen ES, Kotloski R, Denhardt DT, et al. Characterization of osteopontin expression and function after status epilepticus. Epilepsia. 2008;49(10):1675–85. doi: 10.1111/j.1528-1167.2008.01613.x 18522644

94. Weber GF, Ashkar S, Glimcher MJ, Cantor H. Receptor-Ligand Interaction Between CD44 and Osteopontin (Eta-1). Science (New York, NY). 1996;271(5248):509–12.

95. Dzwonek J, Wilczynski GM. CD44: molecular interactions, signaling and functions in the nervous system. Frontiers in Cellular Neuroscience. 2015;9(175).

96. Lerner JT, Sankar R, Mazarati AM. Galanin and epilepsy. Cellular and molecular life sciences: CMLS. 2008;65(12):1864–71. doi: 10.1007/s00018-008-8161-8 18500639

97. Guipponi M, Chentouf A, Webling KEB, Freimann K, Crespel A, Nobile C, et al. Galanin pathogenic mutations in temporal lobe epilepsy. Human Molecular Genetics. 2015;24(11):3082–91. doi: 10.1093/hmg/ddv060 25691535

98. Chang WP, Sudhof TC. SV2 renders primed synaptic vesicles competent for Ca2+ -induced exocytosis. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2009;29(4):883–97.

99. Rogawski MA. A New SV2A Ligand for Epilepsy. Cell. 2016;167(3):587. doi: 10.1016/j.cell.2016.09.057 27768878

100. Crevecoeur J, Kaminski RM, Rogister B, Foerch P, Vandenplas C, Neveux M, et al. Expression pattern of synaptic vesicle protein 2 (SV2) isoforms in patients with temporal lobe epilepsy and hippocampal sclerosis. Neuropathology and applied neurobiology. 2014;40(2):191–204. doi: 10.1111/nan.12054 23617838

101. Dunn AR, Stout KA, Ozawa M, Lohr KM, Hoffman CA, Bernstein AI, et al. Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease. Proc Natl Acad Sci U S A. 2017;114(11):E2253–e62. doi: 10.1073/pnas.1616892114 28246328

102. Jagirdar R, Drexel M, Kirchmair E, Tasan RO, Sperk G. Rapid changes in expression of class I and IV histone deacetylases during epileptogenesis in mouse models of temporal lobe epilepsy. Experimental Neurology. 2015;273:92–104. doi: 10.1016/j.expneurol.2015.07.026 26238735

103. Villagra A, Cheng F, Wang H-W, Suarez I, Glozak M, Maurin M, et al. The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance. Nature immunology. 2009;10(1):92–100. doi: 10.1038/ni.1673 19011628

104. Sng JCG, Taniura H, Yoneda Y. Histone modifications in kainate-induced status epilepticus. European Journal of Neuroscience. 2006;23(5):1269–82. doi: 10.1111/j.1460-9568.2006.04641.x 16553789

105. Iughetti L, Lucaccioni L, Fugetto F, Predieri B, Berardi A, Ferrari F. Brain-derived neurotrophic factor and epilepsy: a systematic review. Neuropeptides. 2018;72:23–9. doi: 10.1016/j.npep.2018.09.005 30262417

106. Kawashima H, Numakawa T, Kumamaru E, Adachi N, Mizuno H, Ninomiya M, et al. Glucocorticoid attenuates brain-derived neurotrophic factor-dependent upregulation of glutamate receptors via the suppression of microRNA-132 expression. Neuroscience. 2010;165(4):1301–11. doi: 10.1016/j.neuroscience.2009.11.057 19958814

107. Jimenez-Mateos EM, Bray I, Sanz-Rodriguez A, Engel T, McKiernan RC, Mouri G, et al. miRNA Expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132. The American journal of pathology. 2011;179(5):2519–32. doi: 10.1016/j.ajpath.2011.07.036 21945804

108. Gangarossa G, Di Benedetto M, O'Sullivan GJ, Dunleavy M, Alcacer C, Bonito-Oliva A, et al. Convulsant doses of a dopamine D1 receptor agonist result in Erk-dependent increases in Zif268 and Arc/Arg3.1 expression in mouse dentate gyrus. PloS one. 2011;6(5):e19415. doi: 10.1371/journal.pone.0019415 21559295

109. Keller D, Erö C, Markram H. Cell Densities in the Mouse Brain: A Systematic Review. Front Neuroanat. 2018;12:83–. doi: 10.3389/fnana.2018.00083 30405363

110. Crouch EE, Doetsch F. FACS isolation of endothelial cells and pericytes from mouse brain microregions. Nature Protocols. 2018;13:738. doi: 10.1038/nprot.2017.158 29565899

111. Barthelson RA, Lambert GM, Vanier C, Lynch RM, Galbraith DW. Comparison of the contributions of the nuclear and cytoplasmic compartments to global gene expression in human cells. BMC Genomics. 2007;8:340. doi: 10.1186/1471-2164-8-340 17894886

112. Bakken TE, Hodge RD, Miller JA, Yao Z, Nguyen TN, Aevermann B, et al. Single-nucleus and single-cell transcriptomes compared in matched cortical cell types. PloS one. 2018;13(12):e0209648. doi: 10.1371/journal.pone.0209648 30586455

113. Grindberg RV, Yee-Greenbaum JL, McConnell MJ, Novotny M, O'Shaughnessy AL, Lambert GM, et al. RNA-sequencing from single nuclei. Proc Natl Acad Sci U S A. 2013;110(49):19802–7. doi: 10.1073/pnas.1319700110 24248345


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2019 Číslo 12