Journal of Molecular Neuroscience

, Volume 50, Issue 2, pp 291–297 | Cite as

Expression Patterns of miR-124, miR-134, miR-132, and miR-21 in an Immature Rat Model and Children with Mesial Temporal Lobe Epilepsy

  • Jing Peng
  • Ahmed Omran
  • Muhammad Usman Ashhab
  • Huimin Kong
  • Na Gan
  • Fang He
  • Fei YinEmail author


Mesial temporal lobe epilepsy (MTLE) is a particularly devastating form of human epilepsy with significant incidence of medical intractability. MicroRNAs (miRs) are small, noncoding RNAs that regulate the posttranscriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of MTLE development. To study the dynamic expression patterns of brain-specific miR-124 and miR-134 and inflammation-related miR-132 and miR-21, we performed qPCR on the hippocampi of immature rats at 25 days of age. Expressions were monitored in the three stages of MTEL and in the control hippocampal tissues corresponding to the same timeframes. A similar expression method was applied to hippocampi obtained from children with MTLE and normal controls. The expression patterns of miR-124 and miR-134 nearly showed the same dynamics in the three stages of MTLE development. On the other hand, miR-132 and miR-21 showed significant upregulation in acute and chronic stages, while in the latent stage, miR-132 was upregulated and miR-21 was downregulated. The four miRs were upregulated in hippocampal tissues obtained from children with MTLE. The significant upregulation of miR-124 and miR-134 in the seizure-related stages and children suggested that both can be potential targets for anticonvulsant drugs in the epileptic developing brains, while the different expression patterns of miR-132 and miR-21 may suggest different functions in MTLE pathogenesis.


Mesial temporal lobe epilepsy miR-124 miR-134 miR-132 miR-21 Developing brains 



This work was kindly supported by the National Natural Science Foundation of China (nos. 30872790, 30901631, 81171226, 81100846) and the Scientific and Technological Department of Hunan Province (2011FJ3163).

Conflict of interest

None of the authors have any conflict of interest to disclose.


  1. Aronica E, Fluiter K, Iyer A, Zurolo E, Vreijling J, van Vliet EA et al (2010) Expression pattern of miR-146a, an inflammation-associated microRNA, in experimental and human temporal lobe epilepsy. Eur J Neurosci 31:1100–1107PubMedCrossRefGoogle Scholar
  2. Berg AT, Shinnar S (1996) Unprovoked seizures in children with febrile seizures: short-term outcome. Neurology 47:562–568PubMedCrossRefGoogle Scholar
  3. Buller B, Liu X, Wang X, Zhang RL, Zhang L, Hozeska-Solgot A et al (2010) MicroRNA-21 protects neurons from ischemic death. FEBS J 277:4299–4307PubMedCrossRefGoogle Scholar
  4. Cascino GD (2009) Temporal lobe epilepsy is a progressive neurologic disorder. Neurology 72:1718–1719PubMedCrossRefGoogle Scholar
  5. Cheng HY, Papp JW, Varlamova O, Dziema H, Russell B, Curfman JP et al (2007) microRNA modulation of circadian-clock period and entrainment. Neuron 54:813–829PubMedCrossRefGoogle Scholar
  6. Choi J, Nordli DR Jr, Alden TD, DiPatri A Jr, Laux L, Kelley K et al (2009) Cellular injury and neuroinflammation in children with chronic intractable epilepsy. J Neuroinflamm 6:38CrossRefGoogle Scholar
  7. Fineberg SK, Kosik KS, Davidson BL (2009) MicroRNAs potentiate neural development. Neuron 64:303–309PubMedCrossRefGoogle Scholar
  8. Hu K, Zhang C, Long L, Long X, Feng L, Li Y et al (2011) Expression profile of microRNAs in rat hippocampus following lithium–pilocarpine-induced status epilepticus. Neurosci Lett 488:252–257PubMedCrossRefGoogle Scholar
  9. Iliopoulos D, Malizos KN, Oikonomou P, Tsezou A (2008) Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks. PLoS One 3:e3740PubMedCrossRefGoogle Scholar
  10. Impey S, Davare M, Lesiak A, Fortin D, Ando H, Varlamova O et al (2010) An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling. Mol Cell Neurosci 43:146–156PubMedCrossRefGoogle Scholar
  11. Isokawa M (2000) Remodeling dendritic spines of dentate granule cells in temporal lobe epilepsy patients and the rat pilocarpine model. Epilepsia 41:14–17CrossRefGoogle Scholar
  12. Jimenez-Mateos EM, Bray I, Sanz-Rodriguez A, Engel T, McKiernan RC, Mouri G et al (2011) miRNA Expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132. Am J Pathol 179:2519–2532PubMedCrossRefGoogle Scholar
  13. Jimenez-Mateos EM, Engel T, Merino-Serrais P, McKiernan RC, Tanaka K, Mouri G et al (2012) Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects. Nat Med 18:1087–1094PubMedCrossRefGoogle Scholar
  14. Kan AA, van Erp S, Derijck AA, de Wit M, Hessel EV, O’Duibhir E et al (2012) Genome-wide microRNA profiling of human temporal lobe epilepsy identifies modulators of the immune response. Cell Mol Life Sci 69:3127–3145PubMedCrossRefGoogle Scholar
  15. Kiezun A, Artzi S, Modai S, Volk N, Isakov O, Shomron N (2012) miRviewer: a multispecies microRNA homologous viewer. BMC Res Notes 5:92PubMedCrossRefGoogle Scholar
  16. Kim J, Krichevsky A, Grad Y, Hayes GD, Kosik KS, Church GM et al (2004) Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Natl Acad Sci 101:360–365PubMedCrossRefGoogle Scholar
  17. Krichevsky AM, King KS, Donahue CP, Khrapko K, Kosik KS (2003) A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9:1274–1281PubMedCrossRefGoogle Scholar
  18. Kulshreshtha R, Ferracin M, Wojcik SE, Garzon R, Alder H, Agosto-Perez FJ et al (2007) A microRNA signature of hypoxia. Mol Cell Biol 27:1859–1867PubMedCrossRefGoogle Scholar
  19. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12:735–739PubMedCrossRefGoogle Scholar
  20. Li KK, Pang JC, Ching AK, Wong CK, Kong X, Wang Y et al (2009) miR-124 is frequently down-regulated in medulloblastoma and is a negative regulator of SLC16A1. Hum Pathol 40:1234–1243PubMedCrossRefGoogle Scholar
  21. Li X, Jin P (2010) Roles of small regulatory RNAs in determining 554 neuronal identity. Nat Rev Neurosci 11:329–338PubMedCrossRefGoogle Scholar
  22. Lu TX, Munitz A, Rothenberg ME (2009) MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. J Immunol 182:4994–5002PubMedCrossRefGoogle Scholar
  23. McKiernan RC, Jimenez-Mateos EM, Bray I, Engel T, Brennan GP, Sano T, Michalak Z et al (2012a) Reduced mature microRNA levels in association with dicer loss in human temporal lobe epilepsy with hippocampal sclerosis. PLoS One 7:35921CrossRefGoogle Scholar
  24. McKiernan RC, Jimenez-Mateos EM, Sano T, Bray I, Stallings RL, Simon RP et al (2012b) Expression profiling the microRNA response to epileptic preconditioning identifies miR-184 as a modulator of seizure-induced neuronal death. Exp Neurol 237:346–354PubMedCrossRefGoogle Scholar
  25. Nudelman AS, DiRocco DP, Lambert TJ, Garelick MG, Le J, Nathanson NM et al (2010) Neuronal activity rapidly induces transcription of the CREB-regulated microRNA-132, in vivo. Hippocampus 20:492–498PubMedGoogle Scholar
  26. Omran A, Elimam D, Shalaby S, Peng J, Yin F (2012a) MicroRNAs: a light into the “Black Box” of neuropediatric diseases? Neuromolecular Med 14:244–261PubMedCrossRefGoogle Scholar
  27. Omran A, Peng J, Zhang C, Xiang QL, Xue J, Gan N et al (2012b) Interleukin-1β and microRNA-146a in an immature rat model and children with mesial temporal lobe epilepsy. Epilepsia 53:1215–1224PubMedCrossRefGoogle Scholar
  28. Peng T, Jia YJ, Wen QQ, Guan WJ, Zhao EY, Zhang BA (2010) Expression of microRNA in neonatal rats with hypoxic-ischemic brain damage. Zhongguo Dang Dai Er Ke Za Zhi 12:373–376PubMedGoogle Scholar
  29. Pichardo-Casas I, Goff LA, Swerdel MR, Athie A, Davila J, Ramos-Brossier M et al (2012) Expression profiling of synaptic microRNAs from the adult rat brain identifies regional differences and seizure-induced dynamic modulation. Brain Res 1436:20–33PubMedCrossRefGoogle Scholar
  30. Pitkänen A, Lukasiuk K (2009) Molecular and cellular basis of epileptogenesis in symptomatic epilepsy. Epilepsy Behav 14:16–25PubMedCrossRefGoogle Scholar
  31. Pitkänen A, Sutula TP (2002) Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol 1:173–181PubMedCrossRefGoogle Scholar
  32. Redell JB, Zhao J, Dash PK (2011) Altered expression of miRNA-21 and its targets in the hippocampus after traumatic brain injury. J Neurosci Res 89:212–221PubMedCrossRefGoogle Scholar
  33. Risbud RM, Lee C, Porter BE (2011) Neurotrophin-3 mRNA a putative target of miR21 following status epilepticus. Brain Res 1424:53–59PubMedCrossRefGoogle Scholar
  34. Sano T, Reynolds JP, Jimenez-Mateos EM, Matsushima S, Taki W, Henshall DC (2012) MicroRNA-34a upregulation during seizure-induced neuronal death. Cell Death Dis 3:287CrossRefGoogle Scholar
  35. Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M et al (2006) A brain-specific microRNA regulates dendritic spine development. Nature 439:283–289PubMedCrossRefGoogle Scholar
  36. Shaked I, Meerson A, Wolf Y, Avni R, Greenberg D, Gilboa-Geffen A et al (2009) MicroRNA-132 potentiates cholinergic anti-inflammatory signaling by targeting acetylcholinesterase. Immunity 31:965–973PubMedCrossRefGoogle Scholar
  37. Smalheiser NR, Lugli G (2009) microRNA regulation of synaptic plasticity. Neuromolecular Med 11:133–140PubMedCrossRefGoogle Scholar
  38. Smirnova L, Grafe A, Seiler A, Schumacher S, Nitsch R, Wulczyn FG (2005) Regulation of miRNA expression during neural cell specification. Eur J Neurosci 21:1469–1477PubMedCrossRefGoogle Scholar
  39. Song YJ, Tian XB, Zhang S, Zhang YX, Li X, Li D et al (2011) Temporal lobe epilepsy induces differential expression of hippocampal miRNAs including let-7e and miR-23a/b. Brain Res 1387:134–140PubMedCrossRefGoogle Scholar
  40. Sonkoly E, Wei T, Janson PC, Sääf A, Lundeberg L, Tengvall-Linder M et al (2007) MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS One 2:e610PubMedCrossRefGoogle Scholar
  41. Soreq H, Wolf Y (2011) NeurimmiRs: microRNAs in the neuroimmune interface. Trends Mol Med 17:548–555PubMedCrossRefGoogle Scholar
  42. Sutula T (2002) Seizure-induced axonal sprouting: assessing connections between injury, local circuits, and epileptogenesis. Epilepsy Curr 2:86–91PubMedCrossRefGoogle Scholar
  43. Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 103:12481–12486PubMedCrossRefGoogle Scholar
  44. Vezzani A, Granata T (2005) Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 46:1724–1743PubMedCrossRefGoogle Scholar
  45. Visvanathan J, Lee S, Lee B, Lee JW, Lee SK (2007) The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. Genes Dev 21:744–749PubMedCrossRefGoogle Scholar
  46. Von Campe G, Spencer DD, de Lanerolle NC (1997) Morphology of dentate granule cells in the human epileptogenic hippocampus. Hippocampus 7:472–488CrossRefGoogle Scholar
  47. Weng H, Shen C, Hirokawa G, Ji X, Takahashi R, Shimada K et al (2011) Plasma miR-124 as a biomarker for cerebral infarction. Biomed Res 32:135–141PubMedCrossRefGoogle Scholar
  48. Wuarin JP, Dudek FE (2001) Excitatory synaptic input to granule cells increases with time after kainite treatment. J Neurophys 85:1067–1077Google Scholar
  49. Zhou J, Wang KC, Wu W, Subramaniam S, Shyy JY, Chiu JJ et al (2011) MicroRNA-21 targets peroxisome proliferators-activated receptor-alpha in an autoregulatory loop to modulate flow-induced endothelial inflammation. Proc Natl Acad Sci USA 108:10355–10360PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Jing Peng
    • 1
  • Ahmed Omran
    • 1
    • 2
  • Muhammad Usman Ashhab
    • 1
  • Huimin Kong
    • 1
  • Na Gan
    • 1
  • Fang He
    • 1
  • Fei Yin
    • 1
    Email author
  1. 1.Department of PediatricsXiangya Hospital of Central South UniversityChangshaChina
  2. 2.Department of Pediatrics and NeonatologySuez Canal UniversityIsmailiaEgypt

Personalised recommendations