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2000
Volume 25, Issue 8
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Objective

The aim of this study was to detect the association between the mTOR-STAT3 pathway and focal cortical dysplasia type IIIa (FCD IIIa) in children.

Methods

A retrospective review was conducted based on 26 pediatric patients diagnosed with FCD IIIa who underwent surgical intervention. These patients were selected from a cohort of 157 individuals presenting with temporal lobe epilepsy. For comparative analysis, a control group consisting of 5 children who underwent intracranial decompression was established. Immunohistochemistry, immunofluorescence, and western blot techniques were used to assess the expression levels of mTOR, P-mTOR, P-70s6k, STAT3, P-STAT3, and GFAP in brain tissue specimens obtained from the two groups.

Results

The mTOR-STAT3 pathway exhibited activation in the FCD IIIa group (all < 0.01). Additionally, immunofluorescence analysis revealed that cells positive for P-STAT3 were identified as astrocytes. Moreover, within the FCD IIIa group, there was a marked elevation in the expression of the mTOR-STAT3 pathway in the hippocampus compared to the brain cortex tissue.

Conclusion

The mTOR-STAT3 pathway was demonstrated to be substantially associated with FCD IIIa in pediatric patients. The activation of the mTOR-STAT3 signaling pathway may contribute to the pathogenesis of FCD IIIa in pediatric patients by modulating the proliferation of astrocytes.

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2024-10-04
2025-11-01

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References

  1. TarkowskiB. KuchcinskaK. BlazejczykM. JaworskiJ. Pathological mTOR mutations impact cortical development.Hum. Mol. Genet.201928132107211910.1093/hmg/ddz042 30789219
     [Google Scholar]
  2. KunY. ZejunD. JianZ. XuelingQ. Surgical histopathologic findings of 232 Chinese children cases with drug-resistant seizures.Brain Behav.2020104e0156510.1002/brb3.1565
     [Google Scholar]
  3. TaylorD.C. FalconerM.A. BrutonC.J. CorsellisJ.A.N. Focal dysplasia of the cerebral cortex in epilepsy.J. Neurol. Neurosurg. Psychiatry197134436938710.1136/jnnp.34.4.369 5096551
     [Google Scholar]
  4. BlümckeI. ThomM. AronicaE. The clinicopathologic spectrum of focal cortical dysplasias: A consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission1.Epilepsia201152115817410.1111/j.1528‑1167.2010.02777.x 21219302
     [Google Scholar]
  5. GiulioniM. MartinoniM. MarucciG. About focal cortical dysplasia (FCD) type IIIa.Epilepsy Res.2014108101955195710.1016/j.eplepsyres.2014.08.002 25178673
     [Google Scholar]
  6. GiulioniM. MarucciG. MartinoniM. Seizure outcome in surgically treated drug-resistant mesial temporal lobe epilepsy based on the recent histopathological classifications.J. Neurosurg.20131191374710.3171/2013.3.JNS122132 23641822
     [Google Scholar]
  7. FauserS. EssangC. AltenmüllerD.M. Is there evidence for clinical differences related to the new classification of temporal lobe cortical dysplasia?Epilepsia201354590991710.1111/epi.12147 23551067
     [Google Scholar]
  8. TahtaA. TurgutM. Focal cortical dysplasia: Etiology, epileptogenesis, classification, clinical presentation, imaging, and management.Childs Nerv. Syst.202036122939294710.1007/s00381‑020‑04851‑9 32766946
     [Google Scholar]
  9. CrinoP.B. mTOR: A pathogenic signaling pathway in developmental brain malformations.Trends Mol. Med.2011171273474210.1016/j.molmed.2011.07.008 21890410
     [Google Scholar]
  10. WongM. A critical review of mTOR inhibitors and epilepsy: From basic science to clinical trials.Expert Rev. Neurother.201313665766910.1586/ern.13.48 23739003
     [Google Scholar]
  11. AlayevA. HolzM.K. mTOR signaling for biological control and cancer.J. Cell. Physiol.201322881658166410.1002/jcp.24351 23460185
     [Google Scholar]
  12. HayN. SonenbergN. Upstream and downstream of mTOR.Genes Dev.200418161926194510.1101/gad.1212704 15314020
     [Google Scholar]
  13. LaplanteM. SabatiniD.M. mTOR signaling at a glance.J. Cell Sci.2009122203589359410.1242/jcs.051011 19812304
     [Google Scholar]
  14. SwitonK. KotulskaK. Janusz-KaminskaA. ZmorzynskaJ. JaworskiJ. Molecular neurobiology of mTOR.Neuroscience201734111215310.1016/j.neuroscience.2016.11.017 27889578
     [Google Scholar]
  15. WongM. CrinoP.B. mTOR and epileptogenesis in developmental brain malformations. In: Noebels JL, Avoli ML, Rogawski MA, Eds. Jasper's Basic Mechanisms of the Epilepsies. 4th ed. Bethesda (MD): National Center for Biotechnology Information (US)2012 22787661
     [Google Scholar]
  16. BarkovichA.J. DobynsW.B. GuerriniR. Malformations of cortical development and epilepsy.Cold Spring Harb. Perspect. Med.201555a02239210.1101/cshperspect.a022392 25934463
     [Google Scholar]
  17. CrinoP.B. mTOR signaling in epilepsy: Insights from malformations of cortical development.Cold Spring Harb. Perspect. Med.201554a02244210.1101/cshperspect.a022442 25833943
     [Google Scholar]
  18. RossiniL. VillaniF. GranataT. FCD Type II and mTOR pathway: Evidence for different mechanisms involved in the pathogenesis of dysmorphic neurons.Epilepsy Res.201712914615610.1016/j.eplepsyres.2016.12.002 28056425
     [Google Scholar]
  19. LimJ.S. KimW. KangH.C. Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy.Nat. Med.201521439540010.1038/nm.3824 25799227
     [Google Scholar]
  20. YokogamiK. WakisakaS. AvruchJ. ReevesS.A. Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR.Curr. Biol.2000101475010.1016/S0960‑9822(99)00268‑7 10660304
     [Google Scholar]
  21. D’AmicoS. ShiJ. MartinB.L. CrawfordH.C. PetrenkoO. ReichN.C. STAT3 is a master regulator of epithelial identity and KRAS-driven tumorigenesis.Genes Dev.20183217-181175118710.1101/gad.311852.118 30135074
     [Google Scholar]
  22. ThaperD. VahidS. KaurR. Galiellalactone inhibits the STAT3/AR signaling axis and suppresses enzalutamide-resistant Prostate Cancer.Sci. Rep.2018811730710.1038/s41598‑018‑35612‑z 30470788
     [Google Scholar]
  23. XuZ. XueT. ZhangZ. Role of signal transducer and activator of transcription-3 in up-regulation of GFAP after epilepsy.Neurochem. Res.201136122208221510.1007/s11064‑011‑0576‑1 21833841
     [Google Scholar]
  24. LuworR.B. StylliS.S. KayeA.H. The role of Stat3 in glioblastoma multiforme.J. Clin. Neurosci.201320790791110.1016/j.jocn.2013.03.006 23688441
     [Google Scholar]
  25. TianD.S. PengJ. MuruganM. Chemokine CCL2–CCR2 signaling induces neuronal cell death via STAT3 activation and IL-1β production after status epilepticus.J. Neurosci.201737337878789210.1523/JNEUROSCI.0315‑17.2017 28716963
     [Google Scholar]
  26. GrabenstatterH.L. Del AngelY.C. CarlsenJ. The effect of STAT3 inhibition on status epilepticus and subsequent spontaneous seizures in the pilocarpine model of acquired epilepsy.Neurobiol. Dis.201462738510.1016/j.nbd.2013.09.003 24051278
     [Google Scholar]
  27. KwanP. ArzimanoglouA. BergA.T. Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies.Epilepsia20105161069107710.1111/j.1528‑1167.2009.02397.x 19889013
     [Google Scholar]
  28. BlümckeI. ThomM. AronicaE. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: A Task Force report from the ILAE Commission on Diagnostic Methods.Epilepsia20135471315132910.1111/epi.12220 23692496
     [Google Scholar]
  29. MengX.F. YuJ.T. SongJ.H. ChiS. TanL. Role of the mTOR signaling pathway in epilepsy.J. Neurol. Sci.20133321-241510.1016/j.jns.2013.05.029
     [Google Scholar]
  30. SaxtonR.A. SabatiniD.M. mTOR signaling in growth, metabolism, and disease.Cell2017169236137110.1016/j.cell.2017.03.035 28388417
     [Google Scholar]
  31. BlümckeI. SarnatH.B. Somatic mutations rather than viral infection classify focal cortical dysplasia type II as mTORopathy.Curr. Opin. Neurol.201629338839510.1097/WCO.0000000000000303 26840044
     [Google Scholar]
  32. RenY. LiuY. WangS. Zhike pingchuan granules improve bronchial asthma by regulating the IL 6/JAK2/STAT3 pathway.Exp. Ther. Med.202122289910.3892/etm.2021.10331 34257712
     [Google Scholar]
  33. WangD.Q. DingX.P. YinS. MaoY.D. Role of the IL-11/STAT3 signaling pathway in human chronic atrophic gastritis and gastric cancer.Genet. Mol. Res.201615210.4238/gmr.15027358 27173233
     [Google Scholar]
  34. LiS.W. WangC.Y. JouY.J. SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway.Sci. Rep.2016612575410.1038/srep25754 27173006
     [Google Scholar]
  35. LuiG.Y. KovacevicZ.V. MenezesS. Novel thiosemicarbazones regulate the signal transducer and activator of transcription 3 (STAT3) pathway: Inhibition of constitutive and interleukin 6-induced activation by iron depletion.Mol. Pharmacol.201587354356010.1124/mol.114.096529 25561562
     [Google Scholar]
  36. LiebleinJ.C. BallS. HutzenB. STAT3 can be activated through paracrine signaling in breast epithelial cells.BMC Cancer20088130210.1186/1471‑2407‑8‑302 18939993
     [Google Scholar]
  37. ZhangZ.H. LiM.Y. WangZ. Convallatoxin promotes apoptosis and inhibits proliferation and angiogenesis through crosstalk between JAK2/STAT3 (T705) and mTOR/STAT3 (S727) signaling pathways in colorectal cancer.Phytomedicine20206815317210.1016/j.phymed.2020.153172 32004989
     [Google Scholar]
  38. SongL. ZhangH. QuX.P. Increased expression of Rho-associated protein kinase 2 confers astroglial Stat3 pathway activation during epileptogenesis.Neurosci. Res.2022177253710.1016/j.neures.2021.10.013 34740726
     [Google Scholar]
  39. TiptonA.E. Cruz Del AngelY. HixsonK. Selective neuronal knockout of STAT3 function inhibits epilepsy progression, improves cognition, and restores dysregulated gene networks in a temporal lobe epilepsy model.Ann. Neurol.202394110612210.1002/ana.26644 36935347
     [Google Scholar]
  40. WangJ.Y. LiW.L. WuJ. Expression of signal transduction and transcriptional activator 3 in children with focal temporal cortical dysplasia IIIa.J Clin Pediatr20143209859862
     [Google Scholar]
/content/journals/cmm/10.2174/0115665240301053240919071840
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Contribution of the Activated mTOR-STAT3 Pathway to the Pathogenesis of Focal Cortical Dysplasia Type IIIa in Pediatric Patients through Astrocyte Proliferation Mediation
Current Molecular Medicine 25, 1048 (2025); https://doi.org/10.2174/0115665240301053240919071840
/content/journals/cmm/10.2174/0115665240301053240919071840
/content/journals/cmm/10.2174/0115665240301053240919071840
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  • Article Type:     Research Article
Keyword(s): Astrocyte; children; focal cortical dysplasia IIIa; GFAP; hippocampus; mTOR-STAT3 pathway

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