Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus

Nature Communications

Volumn 6, Issue , 2015, Pages

  Johnson, Michael R ^a   Behmoaras, Jacques ^b   Bottolo, Leonardo ^a   Krishnan, Michelle L ^c   Pernhorst, Katharina ^d   Santoscoy, Paola L Meza ^e   Rossetti, Tiziana ^b   Speed, Doug ^f   Srivastava, Prashant K ^a,b   Chadeau Hyam, Marc ^a   Hajji, Nabil ^a   Dabrowska, Aleksandra ^a   Rotival, Maxime ^b   Razzaghi, Banafsheh ^b   Kovac, Stjepana ^g   Wanisch, Klaus ^g   Grillo, Federico W ^b   Slaviero, Anna ^b   Langley, Sarah R ^a,b   Shkura, Kirill ^a,b   Roncon, Paolo ^h,i   De, Tisham ^b   Mattheisen, Manuel ^d   Niehusmann, Pitt ^d   O'Brien, Terence J ^j   Petrovski, Slave ^k   Von Lehe, Marec ^l   Hoffmann, Per ^d,m   Eriksson, Johan ^n,o,p   Coffey, Alison J ^q   Cichon, Sven ^d,m   Walker, Matthew ^g   Simonato, Michele ^h,i   Danis, Bénédicte ^r   Mazzuferi, Manuela ^r   Foerch, Patrik ^r   Schoch, Susanne ^d,l   De Paola, Vincenzo ^b   Kaminski, Rafal M ^r   Cunliffe, Vincent T ^e   Becker, Albert J ^d   Petretto, Enrico ^b,s   more..

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b HAMMERSMITH HOSPITAL   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d UNIVERSITY OF BONN   (Germany)

^e UNIVERSITY OF SHEFFIELD   (United Kingdom)

^f UNIVERSITY COLLEGE LONDON   (United Kingdom)

^g UNIVERSITY COLLEGE LONDON   (United Kingdom)

^h UNIVERSITY OF FERRARA   (Italy)

ⁱ National Institute of Neuroscience   (Italy)

^j UNIVERSITY OF MELBOURNE   (Australia)

^k ROYAL MELBOURNE HOSPITAL   (Australia)

^l UNIVERSITY HOSPITAL BONN   (Germany)

^m UNIVERSITY OF BASEL   (Switzerland)

ⁿ FOLKHÄLSAN RESEARCH CENTER   (Finland)

^o HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

^p UNIVERSITY OF HELSINKI   (Finland)

^q WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^r UCB PHARMA   (Belgium)

^s DUKE NUS MEDICAL SCHOOL   (Singapore)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; PROTEIN; SESTRIN 3; TOLL LIKE RECEPTOR; UNCLASSIFIED DRUG; HEAT SHOCK PROTEIN; PENTETRAZOLE; SESN3 PROTEIN, HUMAN;

BRAIN; CYPRINID; DRUG; GENE; GENETICS; NEUROLOGY; PHYSIOLOGY; PROTEIN; SIGNALING;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; FEMALE; GENE IDENTIFICATION; GENE REGULATORY NETWORK; GENETIC ASSOCIATION; GENETIC REGULATION; HIPPOCAMPUS; HUMAN; IN VITRO STUDY; IN VIVO STUDY; MACROPHAGE; MAJOR CLINICAL STUDY; MALE; MICROGLIA; MOUSE; NERVE CELL; NONHUMAN; RNA SEQUENCE; SIGNAL TRANSDUCTION; TEMPORAL LOBE EPILEPSY; ADOLESCENT; ADULT; ANIMAL; CHILD; GENETICS; INFANT; INFLAMMATION; METABOLISM; MIDDLE AGED; MOTOR ACTIVITY; PATHOLOGY; PATHOPHYSIOLOGY; PRESCHOOL CHILD; SEIZURE; YOUNG ADULT; ZEBRA FISH;

DANIO RERIO;

ADOLESCENT; ADULT; ANIMALS; CHILD; CHILD, PRESCHOOL; EPILEPSY, TEMPORAL LOBE; FEMALE; GENE REGULATORY NETWORKS; HEAT-SHOCK PROTEINS; HIPPOCAMPUS; HUMANS; INFANT; INFLAMMATION; MACROPHAGES; MALE; MICE; MICROGLIA; MIDDLE AGED; MOTOR ACTIVITY; NEURONS; PENTYLENETETRAZOLE; SEIZURES; YOUNG ADULT; ZEBRAFISH;

EID: 84923076529     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms7031     Document Type: Article

References (58)

1. Maroso, M. et al. Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nataure Med. 16, 413-419 (2010).
2. Vezzani, A. et al. Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice. Proc. Natl Acad. Sci. USA 97, 11534-11539 (2000).
3. Maroso, M. et al. Interleukin-1beta biosynthesis inhibition reduces acute seizures and drug resistant chronic epileptic activity in mice. Neurotherapeutics 8, 304-315 (2011).
4. Miller, L. L., Pellock, J. M., DeLorenzo, R. J., Meyer, J. M. & Corey, L. A. Univariate genetic analyses of epilepsy and seizures in a population-based twin study: the Virginia Twin Registry. Genet. Epidemiol. 15, 33-49 (1998).
5. Kjeldsen, M. J., Kyvik, K. O., Christensen, K. & Friis, M. L. Genetic and environmental factors in epilepsy: a population-based study of 11900 Danish twin pairs. Epilepsy Res. 44, 167-178 (2001).
6. Speed, D. et al. Describing the genetic architecture of epilepsy through heritability analysis. Brain 137, 2680-2689 (2014).
7. Kasperaviciute, D. et al. Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study. Brain 133, 2136-2147 (2010).
8. Guo, Y. et al. Two-stage genome-wide association study identifies variants in CAMSAP1L1 as susceptibility loci for epilepsy in Chinese. Hum. Mol. Genet. 21, 1184-1189 (2012).
9. EPICURE Consortium et al. Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32. Hum. Mol. Genet. 21, 5359-5372 (2012).
10. Allen, A. S. et al. De novo mutations in epileptic encephalopathies. Nature 501, 217-221 (2013).
11. International League Against Epilepsy Consortium on Complex Epilepsies. Genetic determinants of common epilepsies: a meta-Analysis of genome-wide association studies. Lancet Neurol. 13, 893-903 (2014).
12. Sullivan, P. F., Daly, M. J. & O'Donovan, M. Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nat. Rev. Genet. 13, 537-551 (2012).
13. Guan, Y. et al. Tissue-specific functional networks for prioritizing phenotype and disease genes. PLoS Comput. Biol. 8, e1002694 (2012).
14. Piro, R. M. et al. An atlas of tissue-specific conserved coexpression for functional annotation and disease gene prediction. Eur. J. Hum. Genet. 19, 1173-1180 (2011).
15. Califano, A., Butte, A. J., Friend, S., Ideker, T. & Schadt, E. Leveraging models of cell regulation and GWAS data in integrative network-based association studies. Nature Genet. 44, 841-847 (2012).
16. Bartolomei, F., Chauvel, P. & Wendling, F. Epileptogenicity of brain structures in human temporal lobe epilepsy: a quantified study from intracerebral EEG. Brain 131, 1818-1830 (2008).
17. Civelek, M. & Lusis, A. J. Systems genetics approaches to understand complex traits. Nat. Rev. Genet. 15, 34-48 (2014).
18. Bottolo, L. et al. Bayesian detection of expression quantitative trait loci hot spots. Genetics 189, 1449-1459 (2011).
19. Budanov, A. V., Sablina, A. A., Feinstein, E., Koonin, E. V. & Chumakov, P. M. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science 304, 596-600 (2004).
20. Nogueira, V. et al. Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis. Cancer Cell 14, 458-470 (2008).
21. Zamkova, M., Khromova, N., Kopnin, B. P. & Kopnin, P. Ras-induced ROS upregulation affecting cell proliferation is connected with cell type-specific alterations of HSF1/SESN3/p21Cip1/WAF1 pathways. Cell Cycle 12, 826-836 (2013).
22. Hagenbuchner, J. et al. FOXO3-induced reactive oxygen species are regulated by BCL2L11 (Bim) and SESN3. J. Cell Sci. 125, 1191-1203 (2012).
23. Schafer, J. & Strimmer, K. An empirical Bayes approach to inferring large-scale gene association networks. Bioinformatics 21, 754-764 (2005).
24. Rossin, E. J. et al. Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology. PLoS Genet. 7, e1001273 (2011).
25. Speed, D. et al. A genome-wide association study and biological pathway analysis of epilepsy prognosis in a prospective cohort of newly treated epilepsy. Hum. Mol. Genet. 23, 247-258 (2014).
26. Ravizza, T. et al. The IL-1beta system in epilepsy-Associated malformations of cortical development. Neurobiol. Dis. 24, 128-143 (2006).
27. Mazzuferi, M., Kumar, G., Rospo, C. & Kaminski, R. M. Rapid epileptogenesis in the mouse pilocarpine model: video-EEG, pharmacokinetic and histopathological characterization. Exp. Neurol. 238, 156-167 (2012).
28. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545-15550 (2005).
29. Bottolo, L. et al. ESSp p: a Cp p objected-oriented algorithm for Bayesian stochastic search model exploration. Bioinformatics 27, 587-588 (2011).
30. Gilchrist, M. et al. Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature 441, 173-178 (2006).
31. Cao, D. L. et al. Chemokine CXCL1 enhances inflammatory pain and increases NMDA receptor activity and COX-2 expression in spinal cord neurons via activation of CXCR2. Exp. Neurol. 261C, 328-336 (2014).
32. Ravizza, T. & Vezzani, A. Status epilepticus induces time-dependent neuronal and astrocytic expression of interleukin-1 receptor type I in the rat limbic system. Neuroscience 137, 301-308 (2006).
33. Xanthos, D. N. & Sandkuhler, J. Neurogenic neuroinflammation: inflammatory CNS reactions in response to neuronal activity. Nat. Rev. Neurosci. 15, 43-53 (2014).
34. Baxendale, S. et al. Identification of compounds with novel anti-convulsant properties in a zebrafish model of epileptic seizures. Dis. Models Mech. 5, 773-784 (2012).
35. Baraban, S. C., Taylor, M. R., Castro, P. A. & Baier, H. Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression. Neuroscience 131, 759-768 (2005).
36. Afrikanova, T. et al. Validation of the zebrafish pentylenetetrazol seizure model: locomotor versus electrographic responses to antiepileptic drugs. PLoS One 8, e54166 (2013).
37. Baraban, S. C., Dinday, M. T. & Hortopan, G. A. Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet syndrome treatment. Nat. Commun. 4, 2410 (2013).
38. Zhang, J. et al. c-fos regulates neuronal excitability and survival. Nature Genet. 30, 416-420 (2002).
39. Zhang, B. et al. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer's disease. Cell 153, 707-720 (2013).
40. Heinig, M. et al. A trans-Acting locus regulates an anti-viral expression network and type 1 diabetes risk. Nature 467, 460-464 (2010).
41. Voineagu, I. et al. Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 474, 380-384 (2011).
42. Parikshak, N. N. et al. Integrative functional genomic analyses implicate specific molecular pathways and circuits in autism. Cell 155, 1008-1021 (2013).
43. Vezzani, A., Balosso, S. & Ravizza, T. The role of cytokines in the pathophysiology of epilepsy. Brain. Behav. Immun. 22, 797-803 (2008).
44. Vezzani, A. & Granata, T. Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 46, 1724-1743 (2005).
45. Marchi, N. et al. Efficacy of anti-inflammatory therapy in a model of acute seizures and in a population of pediatric drug resistant epileptics. PLoS One 6, e18200 (2011).
46. Bahcekapili, N. et al. Erythropoietin pretreatment suppresses seizures and prevents the increase in inflammatory mediators during pentylenetetrazoleinduced generalized seizures. Int. J. Neurosci. 124, 762-770 (2014).
47. Papadia, S. et al. Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses. Nat. Neurosci. 11, 476-487 (2008).
48. Chuang, Y. C. et al. Upregulation of nitric oxide synthase II contributes to apoptotic cell death in the hippocampal CA3 subfield via a cytochrome c/caspase-3 signaling cascade following induction of experimental temporal lobe status epilepticus in the rat. Neuropharmacology 52, 1263-1273 (2007).
49. Vezzani, A., French, J., Bartfai, T. & Baram, T. Z. The role of inflammation in epilepsy. Nat. Rev. Neurol. 7, 31-40 (2011).
50. Balosso, S. et al. Molecular and functional interactions between tumor necrosis factor-Alpha receptors and the glutamatergic system in the mouse hippocampus: implications for seizure susceptibility. Neuroscience 161, 293-300 (2009).
51. Galic, M. A. et al. Postnatal inflammation increases seizure susceptibility in adult rats. J. Neurosci. 28, 6904-6913 (2008).
52. Riazi, K. et al. Microglial activation and TNFalpha production mediate altered CNS excitability following peripheral inflammation. Proc. Natl Acad. Sci. USA 105, 17151-17156 (2008).
53. Baram, T. Z. & Hatalski, C. G. Neuropeptide-mediated excitability: a key triggering mechanism for seizure generation in the developing brain. Trends Neurosci. 21, 471-476 (1998).
54. Efron, B. Large-scale simultaneous hypothesis testing: the choice of a null hypothesis. J. Am. Statist. Assoc. 99, 96-104 (2004).
55. Mardia, K. V., Kent, J. T. & Bibby, J. M. Multivariate Analysis (Academic, 1979).
56. Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36 (2013).
57. Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139-140 (2010).
58. Oxtoby, E. & Jowett, T. Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development. Nucleic Acids Res. 21, 1087-1095 (1993).