Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Neuropharmacology
  4. Volume 22, Issue 14
  5. Article
Volume 22, Issue 14
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

Objective

Temporal lobe epilepsy (TLE) is the most common form of refractory focal epilepsy, and the current clinical diagnosis is based on EEG, clinical neurological history and neuroimaging findings.

Methods

So far, there are no blood-based molecular biomarkers of TLE to support clinical diagnosis, despite the pathogenic mechanisms underlying TLE involving defects in the regulation of gene expression. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of gene expression.

Results

Recent studies show the feasibility of detecting miRNAs in body fluids; circulating miRNAs have emerged as potential clinical biomarkers in epilepsy, although the TLE miRNA profile needs to be addressed. Here, we analysed the diagnostic potential of 8 circulating miRNAs in sera of 52 TLE patients and 40 age- and sex-matched donor controls by RT-qPCR analyses.

Conclusion

We found that miR-34a-5p, -106b-5p, -130a-3p, -146a-5p, and -19a-3p are differently expressed in TLE compared to control subjects, suggesting a diagnostic role. Furthermore, we found that miR-34a-5p, -106b-5p, -146a-5p and miR-451a could become prognostic biomarkers, being differentially expressed between drug-resistant and drug-responsive TLE subjects. Therefore, serum miRNAs are diagnostic and drug-resistance predictive molecules of TLE.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cn/10.2174/1570159X22666240516145823
2024-12-01
2024-11-26

  • From This Site

    /content/journals/cn/10.2174/1570159X22666240516145823
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. PeruccaE. FrenchJ. BialerM. Development of new antiepileptic drugs: Challenges, incentives, and recent advances.Lancet Neurol.20076979380410.1016/S1474‑4422(07)70215‑6 17706563
     [Google Scholar]
  2. BrennanG.P. HenshallD.C. MicroRNAs as regulators of brain function and targets for treatment of epilepsy.Nat. Rev. Neurol.202016950651910.1038/s41582‑020‑0369‑8 32546757
     [Google Scholar]
  3. CavaC. MannaI. GambardellaA. BertoliG. CastiglioniI. Potential role of miRNAs as theranostic biomarkers of epilepsy.Mol. Ther. Nucleic Acids20181327529010.1016/j.omtn.2018.09.008 30321815
     [Google Scholar]
  4. AravinA. TuschlT. Identification and characterization of small RNAs involved in RNA silencing.FEBS Lett.2005579265830584010.1016/j.febslet.2005.08.009 16153643
     [Google Scholar]
  5. PfeiferA. LehmannH. Pharmacological potential of RNAi — Focus on miRNA.Pharmacol. Ther.2010126321722710.1016/j.pharmthera.2010.03.006 20388525
     [Google Scholar]
  6. HenshallD.C. MicroRNAs in the pathophysiology and treatment of status epilepticus.Front. Mol. Neurosci.201363710.3389/fnmol.2013.00037 24282394
     [Google Scholar]
  7. EnrightN. SimonatoM. HenshallD.C. Discovery and validation of blood micro RNA s as molecular biomarkers of epilepsy: Ways to close current knowledge gaps.Epilepsia Open20183442743610.1002/epi4.12275 30525113
     [Google Scholar]
  8. ReschkeC.R. HenshallD.C. microRNA and epilepsy.Adv. Exp. Med. Biol.2015888417010.1007/978‑3‑319‑22671‑2_4 26663178
     [Google Scholar]
  9. HuK. XieY.Y. ZhangC. OuyangD.S. LongH.Y. SunD.N. LongL.L. FengL. LiY. XiaoB. MicroRNA expression profile of the hippocampus in a rat model of temporal lobe epilepsy and miR-34a-targeted neuroprotection against hippocampal neurone cell apoptosis post-status epilepticus.BMC Neurosci.201213111510.1186/1471‑2202‑13‑115 22998082
     [Google Scholar]
  10. KanA.A. van ErpS. DerijckA.A.H.A. de WitM. HesselE.V.S. O’DuibhirE. de JagerW. Van RijenP.C. GosselaarP.H. de GraanP.N.E. PasterkampR.J. Genome-wide microRNA profiling of human temporal lobe epilepsy identifies modulators of the immune response.Cell. Mol. Life Sci.201269183127314510.1007/s00018‑012‑0992‑7 22535415
     [Google Scholar]
  11. BotA.M. DębskiK.J. LukasiukK. Alterations in miRNA levels in the dentate gyrus in epileptic rats.PLoS One2013810e7605110.1371/journal.pone.0076051 24146813
     [Google Scholar]
  12. GorterJ.A. IyerA. WhiteI. ColziA. van VlietE.A. SisodiyaS. AronicaE. Hippocampal subregion-specific microRNA expression during epileptogenesis in experimental temporal lobe epilepsy.Neurobiol. Dis.20146250852010.1016/j.nbd.2013.10.026 24184920
     [Google Scholar]
  13. ZhuX. ZhangA. DongJ. YaoY. ZhuM. XuK. Al HamdaM.H. MicroRNA-23a contributes to hippocampal neuronal injuries and spatial memory impairment in an experimental model of temporal lobe epilepsy.Brain Res. Bull.201915217518310.1016/j.brainresbull.2019.07.021 31336125
     [Google Scholar]
  14. SimonatoM. AgostonD.V. Brooks-KayalA. DullaC. FuremanB. HenshallD.C. PitkänenA. TheodoreW.H. TwymanR.E. KobeissyF.H. WangK.K. WhittemoreV. WilcoxK.S. Identification of clinically relevant biomarkers of epileptogenesis — A strategic roadmap.Nat. Rev. Neurol.202117423124210.1038/s41582‑021‑00461‑4 33594276
     [Google Scholar]
  15. WangJ. ZhaoJ. MicroRNA dysregulation in epilepsy: From pathogenetic involvement to diagnostic biomarker and therapeutic agent development.Front. Mol. Neurosci.20211465037210.3389/fnmol.2021.650372 33776649
     [Google Scholar]
  16. GandhiR. HealyB. GholipourT. EgorovaS. MusallamA. HussainM.S. NejadP. PatelB. HeiH. KhouryS. QuintanaF. KivisakkP. ChitnisT. WeinerH.L. Circulating MicroRNAs as biomarkers for disease staging in multiple sclerosis.Ann. Neurol.201373672974010.1002/ana.23880 23494648
     [Google Scholar]
  17. LiuD.Z. TianY. AnderB.P. XuH. StamovaB.S. ZhanX. TurnerR.J. JicklingG. SharpF.R. Brain and blood microRNA expression profiling of ischemic stroke, intracerebral hemorrhage, and kainate seizures.J. Cereb. Blood Flow Metab.20103019210110.1038/jcbfm.2009.186 19724284
     [Google Scholar]
  18. BrennanG.P. HenshallD.C. microRNAs in the pathophysiology of epilepsy.Neurosci. Lett.2018667475210.1016/j.neulet.2017.01.017 28104433
     [Google Scholar]
  19. RineyK. BogaczA. SomervilleE. HirschE. NabboutR. SchefferI.E. ZuberiS.M. AlsaadiT. JainS. FrenchJ. SpecchioN. TrinkaE. WiebeS. AuvinS. Cabral-LimL. NaidooA. PeruccaE. MoshéS.L. WirrellE.C. TinuperP. International league against epilepsy classification and definition of epilepsy syndromes with onset at a variable age: Position statement by the ILAE task force on nosology and definitions.Epilepsia20226361443147410.1111/epi.17240 35503725
     [Google Scholar]
  20. BernasconiA. CendesF. TheodoreW.H. GillR.S. KoeppM.J. HoganR.E. JacksonG.D. FedericoP. LabateA. VaudanoA.E. BlümckeI. RyvlinP. BernasconiN. Recommendations for the use of structural magnetic resonance imaging in the care of patients with epilepsy: A consensus report from the international league against epilepsy neuroimaging task force.Epilepsia20196061054106810.1111/epi.15612 31135062
     [Google Scholar]
  21. JobstB.C. Consensus over individualism: Validation of the ILAE definition for drug resistant epilepsy.Epilepsy Curr.201515417217310.5698/1535‑7511‑15.4.172 26316858
     [Google Scholar]
  22. KokM.G.M. de RondeM.W.J. MoerlandP.D. RuijterJ.M. CreemersE.E. Pinto-SietsmaS.J. Small sample sizes in high-throughput miRNA screens: A common pitfall for the identification of miRNA biomarkers.Biomol Detect. Quantif.2018151510.1016/j.bdq.2017.11.002 29276692
     [Google Scholar]
  23. WangJ. YuJ.T. TanL. TianY. MaJ. TanC.C. WangH.F. LiuY. TanM.S. JiangT. TanL. Genome-wide circulating microRNA expression profiling indicates biomarkers for epilepsy.Sci. Rep.201551952210.1038/srep09522 25825351
     [Google Scholar]
  24. LivakK.J. SchmittgenT.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)).Method. Methods200125440240810.1006/meth.2001.1262 11846609
     [Google Scholar]
  25. MeyerD.D.E. Misc functions of the department of statistics.TU Wien Conference Proceedings2008e1071524
     [Google Scholar]
  26. CavaC. ColapricoA. BertoliG. BontempiG. MauriG. CastiglioniI. How interacting pathways are regulated by miRNAs in breast cancer subtypes.BMC Bioinformatics201617S1234810.1186/s12859‑016‑1196‑1 28185585
     [Google Scholar]
  27. RaoofR. BauerS. El NaggarH. ConnollyN.M.C. BrennanG.P. BrindleyE. HillT. McArdleH. SpainE. ForsterR.J. PrehnJ.H.M. HamerH. DelantyN. RosenowF. MooneyC. HenshallD.C. Dual-center, dual-platform microRNA profiling identifies potential plasma biomarkers of adult temporal lobe epilepsy.EBioMedicine20183812714110.1016/j.ebiom.2018.10.068 30396857
     [Google Scholar]
  28. CavaC. ColapricoA. BertoliG. GraudenziA. SilvaT. OlsenC. NoushmehrH. BontempiG. MauriG. CastiglioniI. SpidermiR: An R/bioconductor package for integrative analysis with miRNA data.Int. J. Mol. Sci.201718227410.3390/ijms18020274 28134831
     [Google Scholar]
  29. MaragkakisM. VergoulisT. AlexiouP. ReczkoM. PlomaritouK. GousisM. KourtisK. KozirisN. DalamagasT. HatzigeorgiouA.G. DIANA-microT web server upgrade supports fly and worm miRNA target prediction and bibliographic miRNA to disease association.Nucleic Acids Res.201139W145W14810.1093/nar/gkr294
     [Google Scholar]
  30. EnrightA.J. JohnB. GaulU. TuschlT. SanderC. MarksD.S. MicroRNA targets in Drosophila.Genome Biol.200351R110.1186/gb‑2003‑5‑1‑r1 14709173
     [Google Scholar]
  31. KrekA. GrünD. PoyM.N. WolfR. RosenbergL. EpsteinE.J. MacMenaminP. da PiedadeI. GunsalusK.C. StoffelM. RajewskyN. Combinatorial microRNA target predictions.Nat. Genet.200537549550010.1038/ng1536 15806104
     [Google Scholar]
  32. BartelD.P. MicroRNAs: Target recognition and regulatory functions.Cell2009136221523310.1016/j.cell.2009.01.002 19167326
     [Google Scholar]
  33. WangX. miRDB: A microRNA target prediction and functional annotation database with a wiki interface.RNA20081461012101710.1261/rna.965408 18426918
     [Google Scholar]
  34. YuG. WangL.G. HanY. HeQ.Y. clusterProfiler: An R package for comparing biological themes among gene clusters.OMICS201216528428710.1089/omi.2011.0118 22455463
     [Google Scholar]
  35. De BenedittisS. FortunatoF. CavaC. GallivanoneF. IaccinoE. CaligiuriM.E. CastiglioniI. BertoliG. MannaI. LabateA. GambardellaA. Circulating microRNAs as potential novel diagnostic biomarkers to predict drug resistance in temporal lobe epilepsy: A pilot study.Int. J. Mol. Sci.202122270210.3390/ijms22020702 33445780
     [Google Scholar]
  36. JuźwikC.A. S Drake, S.; Zhang, Y.; Paradis-Isler, N.; Sylvester, A.; Amar-Zifkin, A.; Douglas, C.; Morquette, B.; Moore, C.S.; Fournier, A.E. microRNA dysregulation in neurodegenerative diseases: A systematic review.Prog. Neurobiol.201918210166410.1016/j.pneurobio.2019.101664 31356849
     [Google Scholar]
  37. YakimovA.M. TimechkoE.E. AreshkinaI.G. UsoltsevaA.A. YakovlevaK.D. KantimirovaE.A. UtyashevN. IvinN. DmitrenkoD.V. MicroRNAs as biomarkers of surgical outcome in mesial temporal lobe epilepsy: A systematic review.Int. J. Mol. Sci.2023246569410.3390/ijms24065694 36982768
     [Google Scholar]
  38. GattásD. NetoF.S.L. Freitas-LimaP. Bonfim-SilvaR. Malaquias de AlmeidaS. de Assis CirinoM.L. Guimarães TiezziD. TirapelliL.F. VelascoT.R. SakamotoA.C. MatiasC.M. CarlottiC.G.Jr TirapelliD.P.C. MicroRNAs miR-629-3p, miR-1202 and miR-1225-5p as potential diagnostic and surgery outcome biomarkers for mesial temporal lobe epilepsy with hippocampal sclerosis.Neurochirurgie202268658358810.1016/j.neuchi.2022.06.002 35700789
     [Google Scholar]
  39. YaoN. SheY. TangS. LiuH. LiuF. MRI features and significance of serum miRNAs and inflammatory cytokines in patients with temporal lobe epilepsy.Concepts Magn. Reson. Part A Bridg. Educ. Res.202220221710.1155/2022/3401838
     [Google Scholar]
  40. SuZ. LiY. ChenS. LiuX. ZhaoK. PengY. ZhouL. Identification of ion channel-related genes and mirna-mrna networks in mesial temporal lobe epilepsy.Front. Genet.20221385352910.3389/fgene.2022.853529 35422840
     [Google Scholar]
  41. LiR. HuJ. CaoS. The clinical significance of mir-135b-5p and its role in the proliferation and apoptosis of hippocampus neurons in children with temporal lobe epilepsy.Dev. Neurosci.2020425-618719410.1159/000512949 33596573
     [Google Scholar]
  42. WuY. ZhangY. ZhuS. TianC. ZhangY. MiRNA-29a serves as a promising diagnostic biomarker in children with temporal lobe epilepsy and regulates seizure-induced cell death and inflammation in hippocampal neurons.Epileptic Disord.202123682383210.1684/epd.2021.1331 34609285
     [Google Scholar]
  43. YuY. DuL. ZhangJ. Febrile seizure-related miR-148a-3p exerts neuroprotection by promoting the proliferation of hippocampal neurons in children with temporal lobe epilepsy.Dev. Neurosci.202143531232010.1159/000518352 34348296
     [Google Scholar]
  44. HuenK. LizarragaD. KogutK. EskenaziB. HollandN. Age-related differences in miRNA expression in mexican-american newborns and children.Int. J. Environ. Res. Public Health201916452410.3390/ijerph16040524 30781749
     [Google Scholar]
  45. WangZ.B. QuJ. YangZ.Y. LiuD.Y. JiangS.L. ZhangY. YangZ.Q. MaoX.Y. LiuZ.Q. Integrated analysis of expression profile and potential pathogenic mechanism of temporal lobe epilepsy with hippocampal sclerosis.Front. Neurosci.20221689202289202210.3389/fnins.2022.892022 35784838
     [Google Scholar]
  46. YuS. GuY. WangT. MuL. WangH. YanS. WangA. WangJ. LiuL. ShenH. NaM. LinZ. Study of neuronal apoptosis cerna network in hippocampal sclerosis of human temporal lobe epilepsy by RNA-seq.Front. Neurosci.20211577062710.3389/fnins.2021.770627 34867172
     [Google Scholar]
  47. LiX. HanY. LiD. YuanH. HuangS. ChenX. QinY. Identification and validation of a dysregulated miRNA-associated mRNA network in temporal lobe epilepsy.BioMed Res. Int.2021202111210.1155/2021/4118216 34722763
     [Google Scholar]
  48. IyerA. ZuroloE. PrabowoA. FluiterK. SplietW.G.M. van RijenP.C. GorterJ.A. AronicaE. MicroRNA-146a: A key regulator of astrocyte-mediated inflammatory response.PLoS One201279e4478910.1371/journal.pone.0044789 23028621
     [Google Scholar]
  49. ZhangK. LindsbergP.J. TatlisumakT. KasteM. OlsenH.S. AnderssonL.C. Stanniocalcin: A molecular guard of neurons during cerebral ischemia.Proc. Natl. Acad. Sci. USA20009773637364210.1073/pnas.97.7.3637 10725397
     [Google Scholar]
  50. MeyerF.B. MoritaA. PuumalaM.R. NicholsD.A. Medical and surgical management of intracranial aneurysms.Mayo Clin. Proc.199570215317210.4065/70.2.153 7845041
     [Google Scholar]
  51. HanJ. GageF.H. A role for miR-19 in the migration of adult-born neurons and schizophrenia.Neurogenesis 201631e125187310.1080/23262133.2016.1251873 28405585
     [Google Scholar]
  52. BielefeldP. MooneyC. HenshallD.C. FitzsimonsC.P. miRNA-mediated regulation of adult hippocampal neurogenesis; Implications for epilepsy.Brain Plast.201731435910.3233/BPL‑160036 29765859
     [Google Scholar]
  53. MathernG.W. PretoriusJ.K. BabbT.L. Quantified patterns of mossy fiber sprouting and neuron densities in hippocampal and lesional seizures.J. Neurosurg.199582221121910.3171/jns.1995.82.2.0211 7815148
     [Google Scholar]
  54. ProperE.A. OestreicherA.B. JansenG.H. VeelenC.W.M. van RijenP.C. GispenW.H. de GraanP.N.E. Immunohistochemical characterization of mossy fibre sprouting in the hippocampus of patients with pharmaco-resistant temporal lobe epilepsy.Brain20001231193010.1093/brain/123.1.19 10611117
     [Google Scholar]
  55. 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 23773767
     [Google Scholar]
  56. ZattoniM. MuraM.L. DeprezF. SchwendenerR.A. EngelhardtB. FreiK. FritschyJ.M. Brain infiltration of leukocytes contributes to the pathophysiology of temporal lobe epilepsy.J. Neurosci.201131114037405010.1523/JNEUROSCI.6210‑10.2011 21411646
     [Google Scholar]
  57. McCormickD.A. ContrerasD. On the cellular and network bases of epileptic seizures.Annu. Rev. Physiol.200163181584610.1146/annurev.physiol.63.1.815 11181977
     [Google Scholar]
  58. GiorgiF.S. BiagioniF. LenziP. FratiA. FornaiF. The role of autophagy in epileptogenesis and in epilepsy-induced neuronal alterations.J. Neural Transm. 2015122684986210.1007/s00702‑014‑1312‑1 25217966
     [Google Scholar]
  59. MasinoS.A. KawamuraM.Jr RuskinD.N. GawrylukJ. ChenX. GeigerJ.D. Purines and the anti-epileptic actions of ketogenic diets.Open Neurosci. J.201041586310.2174/1874082001004010058 22064941
     [Google Scholar]
  60. GreeneR.W. HaasH.L. The electrophysiology of adenosine in the mammalian central nervous system.Prog. Neurobiol.199136432934110.1016/0301‑0082(91)90005‑L 1678539
     [Google Scholar]
  61. Organista-JuárezD. JiménezA. RochaL. Alonso-VanegasM. Guevara-GuzmánR. Differential expression of miR-34a, 451, 1260, 1275 and 1298 in the neocortex of patients with mesial temporal lobe epilepsy.Epilepsy Res.201915710618810.1016/j.eplepsyres.2019.106188 31470144
     [Google Scholar]
  62. ZhangH.L. LinY.H. QuY. ChenQ. The effect of miR-146a gene silencing on drug-resistance and expression of protein of P-gp and MRP1 in epilepsy.Eur. Rev. Med. Pharmacol. Sci.201822823722379 29762840
     [Google Scholar]
  63. LöscherW. GillardM. SandsZ.A. KaminskiR.M. KlitgaardH. Synaptic vesicle glycoprotein 2A ligands in the treatment of epilepsy and beyond.CNS Drugs201630111055107710.1007/s40263‑016‑0384‑x 27752944
     [Google Scholar]
  64. LiY.C. KavalaliE.T. Synaptic vesicle-recycling machinery components as potential therapeutic targets.Pharmacol. Rev.201769214116010.1124/pr.116.013342 28265000
     [Google Scholar]
/content/journals/cn/10.2174/1570159X22666240516145823
Loading
Serum MicroRNAs as Predictors of Diagnosis and Drug-resistance in Temporal Lobe Epilepsy: A Preliminary Study
Curr. Neuropharmacol. 22, 2422 (2024); https://doi.org/10.2174/1570159X22666240516145823
/content/journals/cn/10.2174/1570159X22666240516145823
/content/journals/cn/10.2174/1570159X22666240516145823
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): circulating biomarkers; diagnosis; microRNAs; miRNAs; prediction of therapy response; prognosis; Temporal lobe epilepsy; TLE

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test