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Role of Signal Transducer and Activator of Transcription-3 in Up-Regulation of GFAP After Epilepsy

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Abstract

Glial Fibrillary Acidic Protein (GFAP) is regarded as a marker of reactive astrogliosis. Recent studies have demonstrated that signal transducer and activator of transcription-3, STAT3 regulates GFAP expression after brain injuries. However, whether STAT3 controls astrogliosis in epilepsy is not clear. In this study, we measured p-STAT3 and GFAP expression during the epileptic process using immunohistochemistry, Western blotting and immunofluorescence. Both p-STAT3 and GFAP expression were highly expressed in the rat hippocampus during different phases of the epileptic process. The augmentation of GFAP expression was inhibited by AG490, a janus kinase 2 (JAK2, an upstream gene of STAT3) inhibitor. The coexpression of p-STAT3 and GFAP was detected in the epileptic rat hippocampus and temporal neocortex of patients. These findings indicate that epilepsy involves the activation of STAT3 that up-regulates the expression of GFAP, which may play an important role in epileptogenesis.

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References

  1. Seifert G, Schilling K, Steinhauser C (2006) Astrocyte dysfunction in neurological disorders: a molecular perspective. Nat Rev Neurosci 7(3):194–206

    Article  PubMed  CAS  Google Scholar 

  2. David Y, Cacheaux LP, Ivens S et al (2009) Astrocytic dysfunction in epileptogenesis: consequence of altered potassium and glutamate homeostasis? J Neurosci 29(34):10588–10599

    Article  PubMed  CAS  Google Scholar 

  3. Hawrylak N, Chang FL, Greenough WT (1993) Astrocytic and synaptic response to kindling in hippocampal subfield CA1. II. Synaptogenesis and astrocytic process increases to in vivo kindling. Brain Res 603(2):309–316

    Article  PubMed  CAS  Google Scholar 

  4. Binder DK, Steinhauser C (2006) Functional changes in astroglial cells in epilepsy. Glia 54(5):358–368

    Article  PubMed  Google Scholar 

  5. Levy DE, Darnell JE Jr (2002) Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 3(9):651–662

    Article  PubMed  CAS  Google Scholar 

  6. Brooks-Kayal AR, Raol YH, Russek SJ (2009) Alteration of epileptogenesis genes. Neurotherapeutics 6(2):312–318

    Article  PubMed  CAS  Google Scholar 

  7. Imada K, Leonard WJ (2000) The Jak-STAT pathway. Mol Immunol 37(1–2):1–11

    Article  PubMed  CAS  Google Scholar 

  8. Choi JS, Kim SY, Cha JH et al (2003) Upregulation of gp130 and STAT3 activation in the rat hippocampus following transient forebrain ischemia. Glia 41(3):237–246

    Article  PubMed  Google Scholar 

  9. Gautron L, Lafon P, Chaigniau M et al (2002) Spatiotemporal analysis of signal transducer and activator of transcription 3 activation in rat brain astrocytes and pituitary following peripheral immune challenge. Neuroscience 112(3):717–729

    Article  PubMed  CAS  Google Scholar 

  10. Choi JS, Kim SY, Park HJ et al (2003) Upregulation of gp130 and differential activation of STAT and p42/44 MAPK in the rat hippocampus following kainic acid-induced seizures. Brain Res Mol Brain Res 119(1):10–18

    Article  PubMed  CAS  Google Scholar 

  11. Okamoto OK, Janjoppi L, Bonone FM et al (2010) Whole transcriptome analysis of the hippocampus: toward a molecular portrait of epileptogenesis. BMC Genomics 11:230

    PubMed  Google Scholar 

  12. de la Iglesia N, Puram SV, Bonni A (2009) STAT3 regulation of glioblastoma pathogenesis. Curr Mol Med 9(5):580–590

    Article  Google Scholar 

  13. Fukuda S, Abematsu M, Mori H et al (2007) Potentiation of astrogliogenesis by STAT3-mediated activation of bone morphogenetic protein-Smad signaling in neural stem cells. Mol Cell Biol 27(13):4931–4937

    Article  PubMed  CAS  Google Scholar 

  14. Herrmann JE, Imura T, Song B (2008) STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 28(28):7231–7243

    Article  PubMed  CAS  Google Scholar 

  15. Satriotomo I, Bowen KK, Vemuganti R (2006) JAK2 and STAT3 activation contributes to neuronal damage following transient focal cerebral ischemia. J Neurochem 98(5):1353–1368

    Article  PubMed  CAS  Google Scholar 

  16. Curia G, Longo D, Biagini G et al (2008) The pilocarpine model of temporal lobe epilepsy. J Neurosci Methods 172(2):143–157

    Article  PubMed  CAS  Google Scholar 

  17. Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32(3):281–294

    Article  PubMed  CAS  Google Scholar 

  18. Li YQ, Xue T, Xu J et al (2009) ERK1/2 activation in reactive astrocytes of mice with pilocarpine-induced status epilepticus. Neurol Res 31(10):1108–1114

    Article  PubMed  CAS  Google Scholar 

  19. Ortinski PI, Dong J, Mungenast A et al (2010) Selective induction of astrocytic gliosis generates deficits in neuronal inhibition. Nat Neurosci 13(5):584–591

    Article  PubMed  CAS  Google Scholar 

  20. Khurgel M, Ivy GO (1996) Astrocytes in kindling: relevance to epileptogenesis. Epilepsy Res 26(1):163–175

    Article  PubMed  CAS  Google Scholar 

  21. Briellmann RS, Kalnins RM, Berkovic SF et al (2002) Hippocampal pathology in refractory temporal lobe epilepsy: T2-weighted signal change reflects dentate gliosis. Neurology 58(2):265–271

    PubMed  Google Scholar 

  22. Fellin T, Haydon PG (2005) Do astrocytes contribute to excitation underlying seizures? Trends Mol Med 11(12):530–533

    Article  PubMed  CAS  Google Scholar 

  23. Lauren HB, Lopez-Picon FR, Brandt AM et al (2010) Transcriptome analysis of the hippocampal CA1 pyramidal cell region after kainic acid-induced status epilepticus in juvenile rats. PLoS One 5(5):e10733

    Article  PubMed  Google Scholar 

  24. Xuan YT, Guo Y, Han H et al (2001) An essential role of the JAK-STAT pathway in ischemic preconditioning. Proc Natl Acad Sci USA 98(16):9050–9055

    Article  PubMed  CAS  Google Scholar 

  25. Dziennis S, Jia T, Ronnekleiv OK et al (2007) Role of signal transducer and activator of transcription-3 in estradiol-mediated neuroprotection. J Neurosci 27(27):7268–7274

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Yangmei Chen.

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Zucai Xu and Tao Xue are equal to this article.

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Xu, Z., Xue, T., Zhang, Z. et al. Role of Signal Transducer and Activator of Transcription-3 in Up-Regulation of GFAP After Epilepsy. Neurochem Res 36, 2208–2215 (2011). https://doi.org/10.1007/s11064-011-0576-1

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  • DOI: https://doi.org/10.1007/s11064-011-0576-1

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