Abstract
Background: Recently, microRNAs (miRNAs) have attracted much attention as novel players in the pathogenesis of mesial temporal lobe epilepsy (MTLE) in mature and developing brains. This study aimed to investigate the expression dynamics of miR-9, miR-138, miR-181a, miR-221, and miR-222 in the hippocampus of an immature rat model during the three stages of MTLE development and in children with MTLE. Methodology: qPCR was used to measure expression levels during the three stages of MTLE development (2 h, 3, and 8 weeks after induction of lithium-pilocarpine status epilepticus, representing the acute, latent, and chronic stages, respectively. Expression levels were also measured in hippocampi obtained from children with MTLE and normal controls. Results: In the rat model, miR-9 was significantly upregulated during the acute and chronic stages relative to controls, but not during the latent stage. MiR-138, miR-221 and miR-222 were all downregulated during all three stages of MTLE development. MiR-181a was downregulated during the acute stage, upregulated during the chronic stage, and unaltered during the latent stage. In children, miR-9 and miR-181a were upregulated, while miR-138, miR-221, and miR-222 were downregulated. Conclusion: Modulation of these miRNAs may be a new strategy in designing antiepileptic and anticonvulsant therapies for the developing brain.
[1] Chang B. S., Lowenstein D.H., Epilepsy, N. Engl. J. Med, 2003, 349, 1257–1266 http://dx.doi.org/10.1056/NEJMra02230810.1056/NEJMra022308Search in Google Scholar
[2] Ambros V., microRNAs: Tiny regulators with great potential, Cell, 2001, 107, 823–826 http://dx.doi.org/10.1016/S0092-8674(01)00616-X10.1016/S0092-8674(01)00616-XSearch in Google Scholar
[3] Omran A., Elimam D., Yin F., MicroRNAs: new insights into chronic childhood diseases, Biomed. Res. Int., 2013, 291826 10.1155/2013/291826Search in Google Scholar
[4] Omran A., Elimam D., Shalaby S., Peng J., Yin F., MicroRNAs: a light into the “black box” of neuropediatric diseases?, Neuromolecular. Med., 2012, 14, 244–261 http://dx.doi.org/10.1007/s12017-012-8193-y10.1007/s12017-012-8193-ySearch in Google Scholar
[5] Omran A., Elimam D., Webster K., Shehadeh L., Yin F., MicroRNAs: a new piece in the paediatric cardiovascular disease puzzle, Cardiol. Young, 2013, [Epub ahead of print], doi: 10.1017/ S1047951113000048 Search in Google Scholar
[6] Lagos-Quintana M., Rauhut R., Yalcin A., Meyer J., Lendeckel W., Tuschl T., Identification of tissue-specific microRNAs from mouse, Curr. Biol, 2002, 12, 735–739 http://dx.doi.org/10.1016/S0960-9822(02)00809-610.1016/S0960-9822(02)00809-6Search in Google Scholar
[7] Zhao C., Sun G., Li S., Shi Y., A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination, Nat. Struct. Mol. Biol., 2009, 16, 365–371 http://dx.doi.org/10.1038/nsmb.157610.1038/nsmb.1576Search in Google Scholar PubMed PubMed Central
[8] Bazzoni F., Rossato M., Fabbri M., Gaudiosi D., Mirolo M., Mori L., et al., Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals, Proc. Natl. Acad. Sci. USA, 2009, 106, 5282–5287 http://dx.doi.org/10.1073/pnas.081090910610.1073/pnas.0810909106Search in Google Scholar PubMed PubMed Central
[9] Morton S. U., Scherz P. J., Cordes K. R., Ivey K. N., Stainier D. Y., Srivastava D., microRNA-138 modulates cardiac patterning during embryonic development, Proc. Natl. Acad. Sci. USA, 2008, 105, 17830–17835 http://dx.doi.org/10.1073/pnas.080467310510.1073/pnas.0804673105Search in Google Scholar PubMed PubMed Central
[10] Siegel G., Obernosterer G., Fiore R., Oehmen M., Bicker S., Christensen M., et al., A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis, Nat. Cell. Biol, 2009, 11, 705–716 http://dx.doi.org/10.1038/ncb187610.1038/ncb1876Search in Google Scholar PubMed PubMed Central
[11] Wang Y., Huang J. W., Li M., Cavenee W. K., Mitchell P. S., Zhou X., et al., MicroRNA-138 modulates DNA damage response by repressing histone H2AX expression, Mol. Cancer. Res, 2011, 9, 1100–1111 http://dx.doi.org/10.1158/1541-7786.MCR-11-000710.1158/1541-7786.MCR-11-0007Search in Google Scholar PubMed PubMed Central
[12] Gong H., Song L., Lin C., Liu A., Lin X., Wu J., et al., Downregulation of miR-138 sustains NF-κB activation and promotes lipid raft formation in esophageal squamous cell carcinoma, Clin. Cancer. Res, 2013, 19, 1083–1093 http://dx.doi.org/10.1158/1078-0432.CCR-12-316910.1158/1078-0432.CCR-12-3169Search in Google Scholar
[13] Li Q. J., Chau J., Ebert P. J., Sylvester G., Min H., Liu G., et al., miR-181a is an intrinsic modulator of T cell sensitivity and selection, Cell, 2007, 129, 147–161 http://dx.doi.org/10.1016/j.cell.2007.03.00810.1016/j.cell.2007.03.008Search in Google Scholar
[14] Xie W., Li Z., Li M., Xu N., Zhang Y., miR-181a and inflammation: miRNA homeostasis response to inflammatory stimuli in vivo, Biochem. Biophys. Res. Commun., 2013, 430, 647–652 http://dx.doi.org/10.1016/j.bbrc.2012.11.09710.1016/j.bbrc.2012.11.097Search in Google Scholar
[15] Ouyang Y. B., Lu Y., Yue S., Xu L. J., Xiong X. X., White R. E., et al., miR181 regulates GRP78 and influences outcome from cerebral ischemia in vitro and in vivo, Neurobiol. Dis., 2012, 45, 555–563 http://dx.doi.org/10.1016/j.nbd.2011.09.01210.1016/j.nbd.2011.09.012Search in Google Scholar
[16] Bak M., Silahtaroglu A., Møller M., Christensen M., Rath M. F., Skryabin B., et al., MicroRNA expression in the adult mouse central nervous system, RNA, 2008, 14, 432–434 http://dx.doi.org/10.1261/rna.78310810.1261/rna.783108Search in Google Scholar
[17] Kan A. A., van Erp S., Derijck A. A., de Wit M., Hessel E. V., O’Duibhir E., et al., Genome-wide microRNA profiling of human temporal lobe epilepsy identifies modulators of the immune response, Cell. Mol. Life. Sci., 2012, 69, 3127–3145 http://dx.doi.org/10.1007/s00018-012-0992-710.1007/s00018-012-0992-7Search in Google Scholar
[18] Dietrich J. B., The adhesion molecule ICAM-1 and its regulation in relation with the blood-brain barrier, J. Neuroimmunol., 2002, 128, 58–68 http://dx.doi.org/10.1016/S0165-5728(02)00114-510.1016/S0165-5728(02)00114-5Search in Google Scholar
[19] Racine R. J., Modification of seizure activity by electrical stimulation. II. Motor seizure, Electroencephalogr. Clin. Neurophysiol., 1972, 32, 281–294 http://dx.doi.org/10.1016/0013-4694(72)90177-010.1016/0013-4694(72)90177-0Search in Google Scholar
[20] Ashhab M. U., Omran A., Kong H., Gan N., He F., Peng J., et al., Expressions of tumor necrosis factor Alpha and microRNA-155 in immature rat model of status epilepticus and children with mesial temporal lobe epilepsy. J. Mol. Neurosci., 2013, [Epub ahead of print], doi: 10.1007/s12031-013-0013-9 10.1007/s12031-013-0013-9Search in Google Scholar PubMed
[21] Karafin M., St Louis E. K., Zimmerman M. B., Sparks J. D., Granner M. A., Bimodal ultradian seizure periodicity in human mesial temporal lobe epilepsy, Seizure, 2010, 19, 347–351 http://dx.doi.org/10.1016/j.seizure.2010.05.00510.1016/j.seizure.2010.05.005Search in Google Scholar PubMed PubMed Central
[22] Koh S., Gene expression in immature and mature hippocampus after status epilepticus, In: Schwartzkroin P. (Ed.) Encyclopedia of basic epilepsy research, Academic Press, Oxford, UK, 2009, 227–235 10.1016/B978-012373961-2.00106-5Search in Google Scholar
[23] Bell G. S., Sander J. W., The epidemiology of epilepsy: the size of the problem, Seizure, 2001, 10, 306–314 http://dx.doi.org/10.1053/seiz.2001.058410.1053/seiz.2001.0584Search in Google Scholar
[24] Pitkänen A., Lukasiuk K., Molecular and cellular basis of epileptogenesis in symptomatic epilepsy, Epilepsy. Behav., 2009, 14, 16–25 http://dx.doi.org/10.1016/j.yebeh.2008.09.02310.1016/j.yebeh.2008.09.023Search in Google Scholar
[25] Pitkänen A., Sutula T. P., Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy, Lancet. Neurol., 2001, 1, 173–181 http://dx.doi.org/10.1016/S1474-4422(02)00073-X10.1016/S1474-4422(02)00073-XSearch in Google Scholar
[26] McKiernan R. C., Jimenez-Mateos E. M., Bray I., Engel T., Brennan G. P., Sano T., et al., Reduced mature microRNA levels in association with dicer loss in human temporal lobe epilepsy with hippocampal sclerosis, PLoS One, 2012, 7, e35921 http://dx.doi.org/10.1371/journal.pone.003592110.1371/journal.pone.0035921Search in Google Scholar PubMed PubMed Central
[27] McKiernan R. C., Jimenez-Mateos E. M., Sano T., Bray I., Stallings R. L., Simon R. P., et al., Expression profiling the microRNA response to epileptic preconditioning identifies miR-184 as a modulator of seizure-induced neuronal death, Exp. Neurol., 2012, 237, 346–354 http://dx.doi.org/10.1016/j.expneurol.2012.06.02910.1016/j.expneurol.2012.06.029Search in Google Scholar PubMed PubMed Central
[28] Hu K., Xie Y. Y., Zhang C., Ouyang D. S., Long H. Y., Sun D. N., et al., 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., 2012, 13:115 10.1186/1471-2202-13-115Search in Google Scholar PubMed PubMed Central
[29] Omran A., Peng J., Zhang C., Xiang Q. L., Xue J., Gan N., et al., Interleukin-1β and microRNA-146a in an immature rat model and children with mesial temporal lobe epilepsy, Epilepsia, 2012, 53, 1215–1224 http://dx.doi.org/10.1111/j.1528-1167.2012.03540.x10.1111/j.1528-1167.2012.03540.xSearch in Google Scholar PubMed
[30] Peng J., Omran A., Ashhab M. U., Kong H., Gan N., He F., et al., Expression patterns of miR-124, miR-134, miR-132, and miR-21 in an immature rat model and children with mesial temporal lobe epilepsy, J. Mol. Neurosci., 2013, 50, 291–297 http://dx.doi.org/10.1007/s12031-013-9953-310.1007/s12031-013-9953-3Search in Google Scholar PubMed
[31] Jimenez-Mateos E. M., Engel T., Merino-Serrais P., McKiernan R. C., Tanaka K., Mouri G., et al., Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects, Nat. Med., 2012, 18, 1087–1094 http://dx.doi.org/10.1038/nm.283410.1038/nm.2834Search in Google Scholar PubMed PubMed Central
[32] Jimenez-Mateos E. M., Bray I., Sanz-Rodriguez A., Engel T., McKiernan R. C., Mouri G., et al., miRNA Expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132, Am. J. Pathol., 2011, 179, 2519–2532 http://dx.doi.org/10.1016/j.ajpath.2011.07.03610.1016/j.ajpath.2011.07.036Search in Google Scholar PubMed PubMed Central
[33] Song Y. J., Tian X. B., Zhang S., Zhang Y. X., Li X., Li D., et al., Temporal lobe epilepsy induces differential expression of hippocampal miRNAs including let-7e and miR-23a/b, Brain. Res., 2011, 1387, 134–140 http://dx.doi.org/10.1016/j.brainres.2011.02.07310.1016/j.brainres.2011.02.073Search in Google Scholar PubMed
[34] Lubin F. D., Ren Y., Xu X., Anderson A. E., Nuclear factor-kappa B regulates seizure threshold and gene transcription following convulsant stimulation, J. Neurochem., 2007, 103, 1381–1395 http://dx.doi.org/10.1111/j.1471-4159.2007.04863.x10.1111/j.1471-4159.2007.04863.xSearch in Google Scholar PubMed
[35] Risbud R. M., Porter B. E., Changes in microRNA expression in the whole hippocampus and hippocampal synaptoneurosome fraction following pilocarpine induced status epilepticus, PLoS One, 2013, 8, e53464 http://dx.doi.org/10.1371/journal.pone.005346410.1371/journal.pone.0053464Search in Google Scholar PubMed PubMed Central
[36] Neilson J. R., Zheng G. X., Burge C. B., Sharp P. A., Dynamic regulation of miRNA expression in ordered stages of cellular development, Genes. Dev., 2007, 21, 578–589 http://dx.doi.org/10.1101/gad.152290710.1101/gad.1522907Search in Google Scholar PubMed PubMed Central
© 2013 Versita Warsaw
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.