Hippocampal CA3 Transcriptome Signature Correlates with Initial Precipitating Injury in Refractory Mesial Temporal Lobe Epilepsy

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art_BANDO_Hippocampal_CA3_Transcriptome_Signature_Correlates_with_Initial_Precipitating_2011.PDF (888.31 KB)
Citações na Scopus
25
Tipo de produção
article
Data de publicação
2011
Editora
PUBLIC LIBRARY SCIENCE
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
ALEGRO, Maryana C.
SILVA, Alexandre V.
LIMA, Leandro de A.
Autor de Grupo de pesquisa
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Organizadores
Citação
PLOS ONE, v.6, n.10, article ID e26268, 12p, 2011
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Prolonged febrile seizures constitute an initial precipitating injury (IPI) commonly associated with refractory mesial temporal lobe epilepsy (RMTLE). In order to investigate IPI influence on the transcriptional phenotype underlying RMTLE we comparatively analyzed the transcriptomic signatures of CA3 explants surgically obtained from RMTLE patients with (FS) or without (NFS) febrile seizure history. Texture analyses on MRI images of dentate gyrus were conducted in a subset of surgically removed sclerotic hippocampi for identifying IPI-associated histo-radiological alterations. Methodology/Principal Findings: DNA microarray analysis revealed that CA3 global gene expression differed significantly between FS and NFS subgroups. An integrative functional genomics methodology was used for characterizing the relations between GO biological processes themes and constructing transcriptional interaction networks defining the FS and NFS transcriptomic signatures and its major gene-gene links (hubs). Co-expression network analysis showed that: i) CA3 transcriptomic profiles differ according to the IPI; ii) FS distinctive hubs are mostly linked to glutamatergic signalization while NFS hubs predominantly involve GABAergic pathways and neurotransmission modulation. Both networks have relevant hubs related to nervous system development, what is consistent with cell genesis activity in the hippocampus of RMTLE patients. Moreover, two candidate genes for therapeutic targeting came out from this analysis: SSTR1, a relevant common hub in febrile and afebrile transcriptomes, and CHRM3, due to its putative role in epilepsy susceptibility development. MRI texture analysis allowed an overall accuracy of 90% for pixels correctly classified as belonging to FS or NFS groups. Histological examination revealed that granule cell loss was significantly higher in FS hippocampi. Conclusions/Significance: CA3 transcriptional signatures and dentate gyrus morphology fairly correlate with IPI in RMTLE, indicating that FS-RMTLE represents a distinct phenotype. These findings may shed light on the molecular mechanisms underlying refractory epilepsy phenotypes and contribute to the discovery of novel specific drug targets for therapeutic interventions.
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URI
https://observatorio.fm.usp.br/handle/OPI/22878
Referências
  1. Jamali S, 2006, BRAIN, V129, P625, DOI 10.1093/brain/awl001
  2. HARALICK RM, 1979, P IEEE, V67, P786, DOI 10.1109/PROC.1979.11328
  3. Kassner A, 2010, AM J NEURORADIOL, V31, P809, DOI 10.3174/ajnr.A2061
  4. Munoz A, 2007, EPILEPSIA, V48, P663, DOI 10.1111/j.1528-1167.2007.00986.x
  5. Meyer AC, 2010, B WORLD HEALTH ORGAN, V88, P260, DOI 10.2471/BLT.09.064147
  6. Tallent MK, 1999, J NEUROPHYSIOL, V81, P1626
  7. Bats C, 2007, NEURON, V53, P719, DOI 10.1016/j.neuron.2007.01.030
  8. van Gassen KLI, 2008, EPILEPSIA, V49, P1055, DOI 10.1111/j.1528-1167.2007.01470.x
  9. Gomez O, 2010, J ANAT, V217, P616, DOI 10.1111/j.1469-7580.2010.01291.x
  10. Hallermann S, 2010, NEURON, V68, P710, DOI 10.1016/j.neuron.2010.10.026
  11. Steiner P, 2002, J CELL BIOL, V157, P1197, DOI 10.1083/jcb.200202022
  12. Choi J, 2005, J NEUROSCI, V25, P869, DOI 10.1523/JNEUROSCI.3212-04.2005
  13. Sasikala M., 2008, Journal of Medical Engineering & Technology, V32, P198, DOI 10.1080/03091900701455524
  14. Kao HT, 1999, J EXP ZOOL, V285, P360, DOI 10.1002/(SICI)1097-010X(19991215)285:4<360::AID-JEZ4>3.0.CO;2-3
  15. McClelland S, 2011, NEUROSCI LETT, V497, P155, DOI 10.1016/j.neulet.2011.02.032
  16. Dube C, 2005, ANN NEUROL, V57, P152, DOI 10.1002/ana.20358
  17. Siebzehnrubl FA, 2008, EPILEPSIA, V49, P55, DOI 10.1111/j.1528-1167.2008.01638.x
  18. Alberi S, 2005, MOL CELL NEUROSCI, V29, P313, DOI 10.1016/j.mcn.2005.03.011
  19. Cea-del Rio CA, 2010, J NEUROSCI, V30, P6011, DOI 10.1523/JNEUROSCI.5040-09.2010
  20. MANJUNATH BS, 1991, IEEE T PATTERN ANAL, V13, P478, DOI 10.1109/34.134046
  21. Zook JM, 2005, MAGN RESON IMAGING, V23, P671, DOI 10.1016/j.mri.2005.04.002
  22. Tusher VG, 2001, P NATL ACAD SCI USA, V98, P5116, DOI 10.1073/pnas.091062498
  23. Macdonald RL, 2010, J PHYSIOL-LONDON, V588, P1861, DOI 10.1113/jphysiol.2010.186999
  24. Patel YC, 1999, FRONT NEUROENDOCRIN, V20, P157, DOI 10.1006/frne.1999.0183
  25. Frank T, 2010, NEURON, V68, P724, DOI 10.1016/j.neuron.2010.10.027
  26. Grigorescu SE, 2002, IEEE T IMAGE PROCESS, V11, P1160, DOI 10.1109/TIP.2002.804262
  27. Dube CM, 2010, J NEUROSCI, V30, P7484, DOI 10.1523/JNEUROSCI.0551-10.2010
  28. Zhu L, 2005, J NEUROPHYSIOL, V93, P1557, DOI 10.1152/jn.00616.2004
  29. Goetz R, 2009, J BIOL CHEM, V284, P17883, DOI 10.1074/jbc.M109.001842
  30. Bant JS, 2010, P NATL ACAD SCI USA, V107, P12357, DOI 10.1073/pnas.1005633107
  31. Ma XM, 2003, J NEUROSCI, V23, P10593
  32. Dube CM, 2009, BRAIN DEV-JPN, V31, P366, DOI 10.1016/j.braindev.2008.11.010
  33. Chemin J, 2002, J PHYSIOL-LONDON, V540, P3, DOI 10.1113/jphysiol.2001.013269
  34. Tallent MK, 2008, MOL CELL ENDOCRINOL, V286, P96, DOI 10.1016/j.mce.2007.12.004
  35. Goldfarb M, 2005, CYTOKINE GROWTH F R, V16, P215, DOI 10.1016/j.cytogfr.2005.02.002
  36. Yaffe MB, 1997, CELL, V91, P961, DOI 10.1016/S0092-8674(00)80487-0
  37. Majores M, 2007, EPILEPSIA, V48, P4, DOI 10.1111/j.1528-1167.2007.01062.x
  38. Engel J, 2001, NEUROSCIENTIST, V7, P340
  39. Hattiangady B, 2004, NEUROBIOL DIS, V17, P473, DOI 10.1016/j.nbd.2004.08.008
  40. Abou-Khalil B, 2007, EPILEPSY RES, V73, P104, DOI 10.1016/j.eplepsyres.2006.08.005
  41. Hudson LD, 2011, TRANSGENIC RES, V20, P951, DOI 10.1007/s11248-010-9470-x
  42. Trimbuch T, 2009, CELL, V138, P1222, DOI 10.1016/j.cell.2009.06.050
  43. Scantlebury MH, 2010, EPILEPSY RES, V89, P27, DOI 10.1016/j.eplepsyres.2009.11.002
  44. Stein ELA, 2010, J NEUROCHEM, V113, P42, DOI 10.1111/j.1471-4159.2009.06529.x
  45. Perez-Reyes E, 2006, CELL CALCIUM, V40, P89, DOI 10.1016/j.ceca.2006.04.012
  46. Mandai K, 2009, NEURON, V63, P614, DOI 10.1016/j.neuron.2009.07.031
  47. Mathern GW, 2002, EPILEPSIA, V43, P68, DOI 10.1046/j.1528-1157.43.s.5.28.x
  48. Berg AT, 1999, NEUROLOGY, V53, P1742
  49. Zacharaki EI, 2009, MAGN RESON MED, V62, P1609, DOI 10.1002/mrm.22147
  50. Saeed AI, 2003, BIOTECHNIQUES, V34, P374
  51. Corradini I, 2009, ANN NY ACAD SCI, V1152, P93, DOI 10.1111/j.1749-6632.2008.03995.x
  52. Dube CM, 2007, TRENDS NEUROSCI, V30, P490, DOI 10.1016/j.tins.2007.07.006
  53. Csaba Z, 2005, J NEUROPATH EXP NEUR, V64, P956
  54. Khirug S, 2010, J NEUROSCI, V30, P12028, DOI 10.1523/JNEUROSCI.3154-10.2010
  55. Fiumelli H, 2005, NEURON, V48, P773, DOI 10.1016/j.neuron.2005.10.025
  56. Lee SH, 2011, J PHYSIOL-LONDON, V589, P891, DOI 10.1113/jphysiol.2010.198499
  57. Watanabe TK, 1996, GENOMICS, V38, P273, DOI 10.1006/geno.1996.0628
  58. Lee TS, 2007, MOL MED, V13, P1, DOI 10.2119/2006-00079.Lee
  59. Cendes F, 2004, CURR OPIN NEUROL, V17, P161, DOI 10.1097/01.wco.0000124706.48483.da
  60. Arion D, 2006, NEUROBIOL DIS, V22, P374, DOI 10.1016/j.nbd.2005.12.012
  61. Bae EK, 2010, J CLIN NEUROL, V6, P73, DOI 10.3988/jcn.2010.6.2.73
  62. Baulac S, 2004, LANCET NEUROL, V3, P421, DOI 10.1016/S1474-4422(04)00808-7
  63. Cendes F, 2003, ARQ NEURO-PSIQUIAT, V61, P1
  64. Cho EY, 2009, GENE, V429, P44, DOI 10.1016/j.gene.2008.10.008
  65. Choeiri C, 2005, NEUROSCIENCE, V130, P591, DOI 10.1016/j.neuroscience.2004.09.011
  66. Chu A, 1990, PATTERN RECOGNIT LET, V11, P412
  67. Diaz E, 2010, EUR J NEUROSCI, V32, P261, DOI 10.1111/j.1460-9568.2010.07357.x
  68. Duvernoy HM, 1988, HUMAN HIPPOCAMPUS AT
  69. Ermolinsky B, 2008, NEUROREPORT, V19, P1291, DOI 10.1097/WNR.0b013e3283094bb6
  70. Gasnier B, 2004, PFLUG ARCH EUR J PHY, V447, P756, DOI 10.1007/s00424-003-1091-2
  71. Goodyer CG, 2004, NEUROSCIENCE, V125, P441, DOI 10.1016/j.neuroscience.2004.02.001
  72. Hahn A, 2009, BRAIN DEV-JPN, V31, P515, DOI 10.1016/j.braindev.2009.04.012
  73. Hall M., 2009, SIGKDD EXPLORATIONS, V11, P10, DOI 10.1145/1656274.1656278
  74. Hattiangady B, 2008, EPILEPSIA, V49, P26, DOI 10.1111/j.1528-1167.2008.01635.x
  75. HEUSER K, 2010, EPILEPSY RES, V1, P55
  76. Heuser K, 2011, SEIZURE-EUR J EPILEP, V20, P163, DOI 10.1016/j.seizure.2010.11.015
  77. Kerr N, 2010, MOL CELL NEUROSCI, V44, P165, DOI 10.1016/j.mcn.2010.03.005
  78. Maeda K, 2001, NEUROL MED-CHIR, V41, P582, DOI 10.2176/nmc.41.582
  79. Morales-Corraliza J, 2010, EPILEPSIA, V51, P1910, DOI 10.1111/j.1528-1167.2010.02680.x
  80. Nakayama J, 2009, BRAIN DEV-JPN, V31, P359, DOI 10.1016/j.braindev.2008.11.014
  81. Nielsen JA, 2006, J NEUROSCI, V26, P9881, DOI 10.1523/JNEUROSCI.2246-06.2006
  82. NIELSEN JA, 2009, BMC NEUROSCI, V98
  83. O'Dell C, 2005, PEDIATR NEUROL, V33, P166, DOI 10.1016/j.pediatrneurol.2005.03.005
  84. Ozbas-Gerceker F, 2006, NEUROSCIENCE, V138, P457, DOI 10.1016/j.neuroscience.2005.11.043
  85. Potier S, 2005, EUR J NEUROSCI, V21, P1828, DOI 10.1111/j.1460-9568.2005.04026.x
  86. Romm E, 2005, J NEUROCHEM, V93, P1444, DOI 10.1111/j.1471-4159.2005.03131.x
  87. Singh NA, 2009, PLOS GENET, V5, DOI 10.1371/journal.pgen.1000649
  88. van Gassen KLI, 2009, EPILEPSIA, V50, P957, DOI 10.1111/j.1528-1167.2008.02015.x
  89. Wang YY, 2010, BRAIN PATHOL, V20, P1, DOI 10.1111/j.1750-3639.2008.00254.x
  90. Yao J, 2009, PLOS ONE, V4, DOI 10.1371/journal.pone.0005315

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Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - FM/MPE
Artigos e Materiais de Revistas Científicas - FM/MPS
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InRad
Artigos e Materiais de Revistas Científicas - LIM/23
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