Skip to main content Accessibility help
×
Home

The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity

  • Wei Wang (a1), Xuefeng Wang (a1) (a2), Lang Chen (a1), Yujiao Zhang (a1), Zucai Xu (a1), Jing Liu (a1), Guohui Jiang (a1), Jie Li (a1), Xiaogang Zhang (a1), KeWei Wang (a3), Jinghui Wang (a4), Guojun Chen (a1) and Jing Luo (a1)...

Abstract

miR-124, a brain-specific microRNA, was originally considered as a key regulator in neuronal differentiation and the development of the nervous system. Here we showed that miR-124 expression was suppressed in patients with epilepsy and rats after drug induced-seizures. Intrahippocampal administration of a miR-124 duplex led to alleviated seizure severity and prolonged onset latency in two rat models (pentylenetetrazole- and pilocarpine-induced seizures), while miR-124 inhibitor led to shortened onset latency in pilocarpine-induced seizure rat models. Moreover, the result of local field potentials (LFPs) records further demonstrated miR-124 may have anti-epilepsy function. Inhibition of neuronal firing by miR-124 was associated with the suppression of mEPSC, AMPAR- and NMDAR-mediated currents, which were accompanied by decreased surface expression of NMDAR. In addition, miR-124 injection resulted in decreased activity and expression of cAMP-response element-binding protein1 (CREB1). a key regulator in epileptogenesis. A dual-luciferase reporter assay was used to confirm that miR-124 targeted directly the 3′UTR of CREB1 gene and repressed the CREB1 expression in HEK293T cells. Immunoprecipitation studies confirmed that the CREB1 antibody effectively precipitated CREB1 and NMDAR1 but not GLUR1 from rat brain hippocampus. These results revealed a previously unknown function of miR-124 in neuronal excitability and provided a new insight into molecular mechanisms underlying epilepsy.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity
      Available formats
      ×

Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike licence (http://creativecommons.org/licenses/by-nc-sa/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the same Creative Commons licence is included and the original work is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use.

Corresponding author

*Corresponding author: Jing Luo, Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing 400016, China. E-mail: jgire@163.com

References

Hide All
1. McNamara, J.O. (1999) Emerging insights into the genesis of epilepsy. Nature 399, A15-A22
2. McCormick, D.A. and Contreras, D. (2001) On the cellular and network bases of epileptic seizures. Annual Review of Physiology 63, 815-846
3. Rakhade, S.N. and Jensen, F.E. (2009) Epileptogenesis in the immature brain: emerging mechanisms. Nature Reviews Neurology 5, 380-391
4. McCorry, D., Chadwick, D. and Marson, A. (2004) Current drug treatment of epilepsy in adults. The Lancet Neurology 3, 729-735
5. Simonato, M. et al. (2012) Finding a better drug for epilepsy: preclinical screening strategies and experimental trial design. Epilepsia 53, 1860-1867
6. John, B. et al. (2004) Human microRNA targets. PLoS Biology 2, e363
7. Bartel, D.P. (2009) MicroRNAs: target recognition and regulatory functions. Cell 136, 215-233
8. Sayed, D. and Abdellatif, M. (2011) MicroRNAs in development and disease. Physiological Reviews 91, 827-887
9. Fineberg, S.K., Kosik, K.S. and Davidson, B.L. (2009) MicroRNAs potentiate neural development. Neuron 64(3), 303-309
10. Bhalala, O.G., Srikanth, M. and Kessler, J.A. (2013) The emerging roles of microRNAs in CNS injuries. Nature Reviews Neurology 9(6), 328-339
11. Jimenez-Mateos, E.M. and Henshall, D.C. (2013) Epilepsy and microRNA. Neuroscience 238, 218-229
12. Kosik, K.S. (2006) The neuronal microRNA system. Nature Reviews Neuroscience 7, 911-920
13. Fiore, R. and Schratt, G. (2007) MicroRNAs in vertebrate synapse development. Scientific World Journal 7, 167-177
14. Schratt, G. (2009) microRNAs at the synapse. Nature Reviews Neuroscience 10, 842-849
15. Nudelman, A.S. et al. (2010) Neuronal activity rapidly induces transcription of the CREB-regulated microRNA-132, in vivo. Hippocampus 20, 492-498
16. Jimenez-Mateos, E.M. et al. (2011) miRNA Expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132. The American Journal of Pathology 179, 2519-2532
17. Henshall, D.C. (2013) Antagomirs and microRNA in status epilepticus. Epilepsia 54 (Suppl 6), 17-19
18. Roshan, R.S. et al. (2014) Brain-specific knockdown of miR-29 results in neuronal cell death and ataxia in mice. RNA 20, 1287-1297
19. Lagos-Quintana, M. et al. (2002) Identification of tissue-specific microRNAs from mouse. Current Biology 12, 735-739
20. Deo, M. et al. (2006) Detection of mammalian microRNA expression by in situ hybridization with RNA oligonucleotides. Developmental Dynamics 235, 2538-2548
21. Yu, J.Y. et al. (2008) MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation. Experimental Cell Research 314, 2618-2633
22. Sun, A.X., Crabtree, G.R. and Yoo, A.S. (2013) MicroRNAs: regulators of neuronal fate. Current Opinion in Cell Biology 25(2), 215-221
23. Silber, J. et al. (2008) miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Medicine 6, 14
24. Fowler, A. et al. (2011) miR-124a is frequently down-regulated in glioblastoma and is involved in migration and invasion. European Journal of Cancer 47, 953-963
25. Ponomarev, E.D. et al. (2010) MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-[alpha]-PU. 1 pathway. Nature Medicine 17, 64-70
26. Sonntag, K.C., Woo, T.U.W. and Krichevsky, A.M. (2011) Converging miRNA functions in diverse brain disorders: a case for miR-124 and miR-126. Experimental Neurology 235, 427-435
27. Honchar, M.P., Olney, J.W. and Sherman, W.R. (1983) Systemic cholinergic agents induce seizures and brain damage in lithium-treated rats. Science 220, 323-325
28. Cavalheiro, E.A., Santos, N.F. and Priel, M.R. (1996) The pilocarpine model of epilepsy in mice. Epilepsia 37, 1015-1019
29. Racine, R.J. (1972) Modification of seizure activity by electrical stimulation: II. Motor seizure. Electroencephalography and Clinical Neurophysiology 32, 281-294
30. Kanter-Schlifke, I. et al. (2007) Brain area, age and viral vector-specific glial cell-line-derived neurotrophic factor expression and transport in rat. Neuroreport 18, 845-850
31. Hou, J. et al. (2011) Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell 19, 232-243
32. Davis, C.J. et al. (2011) MicroRNA 132 alters sleep and varies with time in brain. Journal of Applied Physiology 111, 665-72
33. Zhang, R. et al. (2014) MicroRNA-377 inhibited proliferation and invasion of human glioblastoma cells by directly targeting specificity protein 1. Neuro Oncology 16, 1510-1522
34. Schmoll, H. et al. (2003) Kindling status in sprague-dawley rats induced by pentylenetetrazole: involvement of a critical development period. The American Journal of Pathology 162, 1027-1034
35. Fang, M. et al. (2011) Increased expression of Sonic hedgehog in temporal lobe epileptic foci in humans and experimental rats. Neuroscience 182, 62-70
36. Gassmann, M. et al. (2009) Quantifying Western blots: pitfalls of densitometry. Electrophoresis 30, 1845-1855
37. Zhang, Y. et al. (2015) Involvement of sigma-1 receptor in astrocyte activation induced by methamphetamine via up-regulation of its own expression. Journal of Neuroinflammation 17, 12, 29
38. Liu, M. et al. (2011) miR-185 targets RhoA and Cdc42 expression and inhibits the proliferation potential of human colorectal cells. Cancer Letters 301, 151-160
39. Yin, H. et al. (2011) Upregulation of liprin-α1 protein in the temporal neocortex of intractable epileptic patients and experimental rats. Synapse 65, 742-750
40. Wu, P., Jiang, L. and Chen, H.S. (2010) Sodium valproate at the therapeutic concentration inhibits the induction but not the maintenance phase of long-term potentiation in rat hippocampal CA1 area. Biochemical and Biophysical Research Communications 391, 582-586
41. Zhong, P. et al. (2003) Impaired modulation of GABAergic transmission by muscarinic receptors in a mouse transgenic model of Alzheimer's disease. Journal of Biological Chemistry 278, 26888-26896
42. Chen, G. et al. (2006) Dopamine D3 receptors regulate GABAA receptor function through a phospho-dependent endocytosis mechanism in nucleus accumbens. The Journal of Neuroscience 26, 2513-2521
43. Gean, P.W. and Shinnick-Gallagher, P. (1988) Characterization of the epileptiform activity induced by magnesium-free solution in rat amygdala slices: an intracellular study. Experimental Neurology 101, 248-255
44. Jimenez-Mateos, E.M. et al. (2012) Silencing microRNA-134 produces neuroprotective and prolonged seizuresuppressive effects. Nature Medicine 18, 1087-1094
45. Cao, Q. et al. (2016) Elevated Expression of Acid-Sensing Ion Channel 3 Inhibits Epilepsy via Activation of Interneurons. Molecular Neurobiology 53, 485-498
46. Wang, H. et al. (2015) MiR-124 regulates apoptosis and autophagy process in MPTP model of Parkinson's disease by targeting to Bim. Brain Pathology. doi: 10.1111/bpa.12267
47. Zhang, H. et al. (2013) MIR-124 inhibits the migration and invasion of ovarian cancer cells by targeting SphK1. Journal of Ovarian Research 6, 84
48. An, L. et al. (2013) microRNA-124 inhibits migration and invasion by down-regulating ROCK1 in glioma. PLoS One 8, e69478
49. Rajasethupathy, P. et al. (2009) Characterization of small RNAs in Aplysia reveals a role for miR-124 in constraining synaptic plasticity through CREB. Neuron 63, 803-817
50. Preethi, J. et al. (2012) Participation of microRNA 124-CREB pathway: a parallel memory enhancing mechanism of standardised extract of Bacopa monniera (BESEB CDRI-08). Neurochemical Research 37, 2167-2177
51. Rakhade, S.N. et al. (2005) A common pattern of persistent gene activation in human neocortical epileptic foci. Annals of Neurology 58, 736-747
52. Zhu, X. et al. (2012) Decreased CREB levels suppress epilepsy. Neurobiology of Disease 45, 253-263
53. Kan, A.A. et al. (2012) Genome-wide microRNA profiling of human temporal lobe epilepsy identifies modulators of the immune response. Cellular and Molecular Life Sciences 69, 3127-3145
54. Hu, K. et al. (2011) Expression profile of microRNAs in rat hippocampus following lithium–pilocarpine-induced status epilepticus. Neuroscience Letters 488, 252-257
55. Willemen, H. et al. (2012) MicroRNA-124 as a novel treatment for persistent hyperalgesia. Journal of Neuroinflammation 9, 143
56. Brodie, M.J. (2010) Antiepileptic drug therapy the story so far. Seizure 19, 650-655
57. Clark, A.M. et al. (2010) The microRNA miR-124 controls gene expression in the sensory nervous system of Caenorhabditis elegans. Nucleic Acids Research 38, 3780-3793
58. Huang, Y.H. et al. (2008) CREB modulates the functional output of nucleus accumbens neurons. Journal of Biological Chemistry 283, 2751-2760
59. Marie, H. et al. (2005) Generation of silent synapses by acute in vivo expression of CaMKIV and CREB. Neuron 45, 741-752

The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity

  • Wei Wang (a1), Xuefeng Wang (a1) (a2), Lang Chen (a1), Yujiao Zhang (a1), Zucai Xu (a1), Jing Liu (a1), Guohui Jiang (a1), Jie Li (a1), Xiaogang Zhang (a1), KeWei Wang (a3), Jinghui Wang (a4), Guojun Chen (a1) and Jing Luo (a1)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed