The dynamic expressional changes of neuronal growth and differentiation-associated miR-124a and miR-9 in the process of epileptogenesis_Journal of Epilepsy

Authors：

 HUKai , LONGLili , FENGLi , XIEYuanyuan , LongHongyu ,  XIAOBo

Department of Neurology, Xiangya Hospital of Central South University, Changsha 410008, China;

Corresponding author：

XIAOBo, Email: xiaobo_xy@126.com

Keywords：

Epilepsy; Status epilepticus; miRNAs; Hippocampus; Neurogenesis; Growth and differentiation

DOI：

10.7507/2096-0247.20160042

Video：

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Objective To explore the dynamic expression changes of neuronal growth and differentiation-associated miR-124a and miR-9 in the process of epileptogenesis. Methods Establish the lithium-pilocarpine induced status epilepticus (SE) rat model. Animal behavior change induced by SE as well as in the period of chronic epilepsy was observed by naked-eye or video-recording. Major time points for the study were chosen at 1d, 7d, 14d and 28d post-SE, on which the post-SE rats were decapitated and their hippocampal specimens were obtained. Total RNA from each specimen was extracted and qPCR was exploited to detect miR-124a and miR-9 expression in the specimens. Statistical analysis was used to show the dynamic expressional changes of miR-124a and miR-9 in rat hippocampus at 1d, 7d, 14d and 28d post-SE during the process of epileptogenesis. Results Compared with normal rats, the expression level of miR-124a in rat hippocampus did not show a significant difference at 1d post-SE, but it had shown markedly differences at 7d, 14d and 28d post-SE(P < 0.05), with a declining trend. Compared with normal rats, the expression level of miR-9 had demonstrated significant differences at 1d, 7d, 14d and 28d post-SE(P < 0.05)with a generally increasing trend, although there was slight fluctuation of expressional up-regulation at 7d post-SE. Conclusion Neuronal growth and differentiation-associated miR-124a and miR-9 had shown dynamic changes of down-regulation or up-regulation in the process of epileptogenesis. It can be suspected that miR-124a and miR-9 take part in hippocampal neurogenesis post-SE and be involved in epileptogenesis process.

Citation： HUKai, LONGLili, FENGLi, XIEYuanyuan, LongHongyu, XIAOBo. The dynamic expressional changes of neuronal growth and differentiation-associated miR-124a and miR-9 in the process of epileptogenesis. Journal of Epilepsy, 2016, 2(3): 224-228. doi: 10.7507/2096-0247.20160042 Copy

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2.	Scharfman HE, Goodman JH, Sollas AL. Granule-like neurons at the hilar/CA3 border after status epilepticus and their synchrony with area CA3pyramidal cells:functional implications of seizure-induced neurogenesis. J Neurosci, 2000, 20(16):6144-6158.
3.	Pirttilä TJ, Lukasiuk K, Håkansson K, et al. Cystatin cmodulates neurodegeneration and neurogenesis following status epilepticus in mouse. Neurobiol Dis, 2005, 20(2):241-253.
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10.	Hu K, Zhang C, Long L, et al. Expression profile of microRNAs in rat hippocampus following lithium-pilocarpine-induced status epilepticus. Neurosci Lett, 2011, 488(3):252-257.
11.	Hu K, Xie YY, Zhang C, et al. MicroRNA expression profile of the hippocampus in a rat model of temporal lobe epilepsy and miR-34a-targetedneuroprotection against hippocampal neurone cell apoptosis post-status epilepticus. BMC Neurosci, 2012, 22(2):113-115.
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13.	Jimenez-Mateos EM, Engel T, Merino-Serrais P, et al. Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects. Nat Med, 2012, 18(7):1087-1094.
14.	Jimenez-Mateos EM, Bray I, Sanz-Rodriguez A, et al. miRNA Expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132. Am J Pathol, 2011, 179(5):2519-2532.
15.	Cheng LC, Pastrana E, Tavazoie M, et al. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci, 2009, 12(4):399-408.
16.	Liu C, Zhao X. MicroRNAs in adult and embryonic neurogenesis. Neuromolecular Med, 2009, 11(3):141-152.
17.	高杰, 邓艳春.海马硬化与癫痫.癫痫杂志, 2016, 2(1):64-66.
18.	周艺, 罗朝晖, 贺星惠, 等. Robo3在颞叶癫痫大鼠模型中的动态表达研究.癫痫杂志, 2016, 2(1):34-37.
19.	Krichevsky AM, Sonntag KC, Isacson O, et al. Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells, 2006, 24(4):857-864.
20.	Zhao C, Sun G, Li S, et al. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fatedetermination. Nat Struct Mol Biol, 2009, 16(4):365-371.

1. Parent JM, Elliott RC, Pleasure SJ, et al. Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. Ann Neurol, 2006, 59(1):81-91.
2. Scharfman HE, Goodman JH, Sollas AL. Granule-like neurons at the hilar/CA3 border after status epilepticus and their synchrony with area CA3pyramidal cells:functional implications of seizure-induced neurogenesis. J Neurosci, 2000, 20(16):6144-6158.
3. Pirttilä TJ, Lukasiuk K, Håkansson K, et al. Cystatin cmodulates neurodegeneration and neurogenesis following status epilepticus in mouse. Neurobiol Dis, 2005, 20(2):241-253.
4. Luskin MB. Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricularzone. Neuron, 1993, 11(1):173-189.
5. Kuhn HG, Dickinson-Anson H, Gage FH. Neurogenesis in the dentate gyrus of the adult rat:age-related decrease of neuronal progenitor proliferation. J Neurosci, 1996, 16(6):2027-2033.
6. Kee N, Teixeira CM, Wang AH, et al. Imaging activation of adult-generated granule cells in spatial memory. Nat Protoc, 2007, 2(12):3033-3044.
7. Toni N, Sultan S. Synapse formation on adult-born hippocampal neurons. Eur J Neurosci, 2011, 33(6):1062-1068.
8. Kim VN, Nam JW. Genomics of microRNA. Trends Genet, 2006, 22(3):165-1673.
9. Wienholds E, Kloosterman WP, Miska E, et al. MicroRNA expression in zebrafish embryonic development. Science, 2005, 309(5732):310-311.
10. Hu K, Zhang C, Long L, et al. Expression profile of microRNAs in rat hippocampus following lithium-pilocarpine-induced status epilepticus. Neurosci Lett, 2011, 488(3):252-257.
11. Hu K, Xie YY, Zhang C, et al. MicroRNA expression profile of the hippocampus in a rat model of temporal lobe epilepsy and miR-34a-targetedneuroprotection against hippocampal neurone cell apoptosis post-status epilepticus. BMC Neurosci, 2012, 22(2):113-115.
12. Aronica E, Fluiter K, Iyer A, et al. Expression pattern of miR-146a, an inflammation-associated microRNA, in experimental and human temporal lobe epilepsy. Eur J Neurosci, 2010, 31(6):1100-1107.
13. Jimenez-Mateos EM, Engel T, Merino-Serrais P, et al. Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects. Nat Med, 2012, 18(7):1087-1094.
14. Jimenez-Mateos EM, Bray I, Sanz-Rodriguez A, et al. miRNA Expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132. Am J Pathol, 2011, 179(5):2519-2532.
15. Cheng LC, Pastrana E, Tavazoie M, et al. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci, 2009, 12(4):399-408.
16. Liu C, Zhao X. MicroRNAs in adult and embryonic neurogenesis. Neuromolecular Med, 2009, 11(3):141-152.
17. 高杰, 邓艳春.海马硬化与癫痫.癫痫杂志, 2016, 2(1):64-66.
18. 周艺, 罗朝晖, 贺星惠, 等. Robo3在颞叶癫痫大鼠模型中的动态表达研究.癫痫杂志, 2016, 2(1):34-37.
19. Krichevsky AM, Sonntag KC, Isacson O, et al. Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells, 2006, 24(4):857-864.
20. Zhao C, Sun G, Li S, et al. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fatedetermination. Nat Struct Mol Biol, 2009, 16(4):365-371.

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The dynamic expressional changes of neuronal growth and differentiation-associated miR-124a and miR-9 in the process of epileptogenesis

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