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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

MicroRNA-451 Aggravates Kainic Acid-induced Seizure and Neuronal Apoptosis by Targeting GDNF

Author(s): Ning Weng, Jingbo Sun, Shixiang Kuang, Hai Lan, Qiansong He, Hui Yang, Lin Zhang and Hong Xue*

Volume 17, Issue 1, 2020

Page: [50 - 57] Pages: 8

DOI: 10.2174/1567202617666191223150510

Price: $65

Abstract

Aim: Epilepsy is a common and serious neurological disease that causes recurrent episodes, but its molecular mechanism remains unclear. Abnormal miRNA expression is associated with epilepsy, including miR-451. This research investigated the role of miR-451 in seizure and its detailed mechanism.

Methods: The seizure mice model was induced by kainic acid (KA) injection to the right lateral cerebral ventricle. Behavioral changes in mice were observed and evaluated by the Racine Scale. The miR-451 knockout mice were established by adenovirus infection. The in vitro model was performed by miR-451 mimics transfected HEK-293 cells. The amount of neuronal death and morphological changes were evaluated by Nissl staining and H&E staining.

Results: The results showed that miR-451 is up regulated in KA-induced seizure models and miR- 451 knockout decreased the behavior score and improved the pathological changes of the hippocampus. Besides, MiR-451 knockout inhibited the apoptosis of hippocampal neurons. Bioinformatics studies have shown that glial cell line-derived neurotrophic factor (GDNF) is a target gene of miR-451. MiR-451 could negatively regulate the expression of GDNF. GDNF overexpression could reverse the effect of miR-451 on KA induced brain injury and neuronal apoptosis.

Conclusion: This research demonstrates that miR-451 can affect the behavior of KA-induced epilepsy mice and hippocampal neuronal damage by regulating GDNF expression. The results would provide an experimental foundation for further research about the potential contribution of mi- RNAs to epilepsy pathophysiology.

Keywords: MicroRNA-451, seizure, glial cell line-derived neurotrophic factor (GDNF), neuronal apoptosis, epilepsy, HEK-293 cells.

« Previous Next »
[1]
Thurman, D.J.; Beghi, E.; Begley, C.E. Standards for epidemiologic studies and surveillance of epilepsy. Epilepsia, 2011, 52(s7), 2-26.
[http://dx.doi.org/10.1111/j.1528-1167.2011.03121.x]
[2]
Naderali, E.; Nikbakht, F.; Ofogh, S.N.; Rasoolijazi, H. The role of rosemary extract in degeneration of hippocampal neurons induced by kainic acid in the rat: A behavioral and histochemical approach. J. Integr. Neurosci., 2018, 17(1), 19-25.
[http://dx.doi.org/10.3233/JIN-170035] [PMID: 29376880]
[3]
Eadie, M.J. Shortcomings in the current treatment of epilepsy. Expert Rev. Neurother., 2012, 12(12), 1419-1427.
[http://dx.doi.org/10.1586/ern.12.129] [PMID: 23237349]
[4]
Tomari, S.; Tanaka, T.; Ihara, M. Risk factors for post-stroke seizure recurrence after the first episode. Seizure, 2017, 52, 22-26.
[http://dx.doi.org/10.1016/j.seizure.2017.09.007] [PMID: 28957721]
[5]
Maes, O.C.; Chertkow, H.M.; Wang, E.; Schipper, H.M. MicroRNA: Implications for Alzheimer disease and other Human CNS Disorders. Curr. Genomics, 2009, 10(3), 154-168.
[http://dx.doi.org/10.2174/138920209788185252] [PMID: 19881909]
[6]
Huang, Y.; Shen, X.J.; Zou, Q. Biological functions of microRNAs. RE:view, 2011, 67(1), 129-139.
[http://dx.doi.org/10.1007/s13105-010-0050-6]
[7]
Hu, K.; Zhang, C.; Long, L. Expression profile of microRNAs in rat hippocampus following lithium-pilocarpine-induced status epilepticus. Neurosci. Lett., 2011, 488(3), 252-257.
[http://dx.doi.org/10.1016/j.neulet.2010.11.040] [PMID: 21094214]
[8]
Aronica, E.; Fluiter, K.; Iyer, A. Expression pattern of miR-146a, an inflammation-associated microRNA, experimental and human temporal lobe epilepsy. Eur. J. Neurosci., 2010, 31(6), 1100-1107.
[http://dx.doi.org/10.1111/j.1460-9568.2010.07122.x]
[9]
Henshall, D.C.; Hamer, H.M.; Pasterkamp, R.J. MicroRNAs in epilepsy: Pathophysiology and clinical utility. Lancet Neurol., 2016, 15(13), 1368-1376.
[http://dx.doi.org/10.1016/S1474-4422(16)30246-0] [PMID: 27839653]
[10]
Jimenez-Mateos, E.M.; Engel, T.; Merino-Serrais, P. Antagomirs targeting microRNA-134 increase hippocampal pyramidal neuron spine volume in vivo and protect against pilocarpine-induced status epilepticus. Brain Struct. Funct., 2015, 220(4), 2387-2399.
[http://dx.doi.org/10.1007/s00429-014-0798-5]
[11]
Cai, Z.; Li, S.; Li, S. Antagonist targeting microRNA-155 protects against lithium-pilocarpine-induced status epilepticus in C57BL/6 mice by activating brain-derived neurotrophic factor. Front. Pharmacol., 2016, 7, 129.
[12]
Li, Y-J; Ping, C; Tang, J MicroRNA-455 suppresses non-small cell lung cancer through targeting ZEB1 2016; 40(6): 621-8.
[13]
Nan, Y.; Han, L.; Zhang, A. MiRNA-451 plays a role as tumor suppressor in human glioma cells. Brain Res., 2010, 1359, 14-21.
[http://dx.doi.org/10.1016/j.brainres.2010.08.074] [PMID: 20816946]
[14]
Godlewski, J.; Nowicki, M.O.; Bronisz, A. MicroRNA-451 regulates LKB1/AMPK signaling and allows adaptation to metabolic stress in glioma cells. Mol. Cell, 2010, 37(5), 620-632.
[http://dx.doi.org/10.1016/j.molcel.2010.02.018] [PMID: 20227367]
[15]
Alural, B.; Duran, G.A.; Tufekci, K.U. EPO mediates neurotrophic, neuroprotective, anti-oxidant, and anti-apoptotic effects via downregulation of miR-451 and miR-885-5p in SH-SY5Y neuron-like cells. Front. Immunol., 2014, 5, 475.
[16]
Liu, Q.; Hu, Y.; Zhang, M.; Yan, Y.; Yu, H.; Ge, L. microRNA-451 protects neurons against ischemia/reperfusion injury-induced cell death by targeting CELF2. Neuropsychiatr. Dis. Treat., 2018, 14, 2773-2782.
[http://dx.doi.org/10.2147/NDT.S173632] [PMID: 30425495]
[17]
Racine, R.J. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr. Clin. Neurophysiol., 1972, 32(3), 281-294.
[http://dx.doi.org/10.1016/0013-4694(72)90177-0] [PMID: 4110397]
[18]
Lapchak, P.A.; Araujo, D.M.; Hilt, D.C.; Sheng, J.; Jiao, S. Adenoviral vector-mediated GDNF gene therapy in a rodent lesion model of late stage Parkinson’s disease. Brain Res., 1997, 777(1-2), 153-160.
[http://dx.doi.org/10.1016/S0006-8993(97)01100-1] [PMID: 9449424]
[19]
Xie, J.; Hu, X.; Yi, C.; Hu, G.; Zhou, X.; Jiang, H. MicroRNA 451 protects against cardiomyocyte anoxia/reoxygenation injury by inhibiting high mobility group box 1 expression. Mol. Med. Rep., 2016, 13(6), 5335-5341.
[http://dx.doi.org/10.3892/mmr.2016.5192] [PMID: 27121079]
[20]
Zhu, H.; Wu, H.; Liu, X. Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem. Pharmacol., 2008, 76(5), 582-588.
[http://dx.doi.org/10.1016/j.bcp.2008.06.007] [PMID: 18619946]
[21]
Li, M-M.; Li, X-M.; Zheng, X-P.; Yu, J.T.; Tan, L. MicroRNAs dysregulation in epilepsy. Brain Res., 2014, 1584, 94-104.
[http://dx.doi.org/10.1016/j.brainres.2013.09.049] [PMID: 24096213]
[22]
Ogawa, D.; Ansari, K.; Nowicki, M.O. MicroRNA-451 inhibits migration of glioblastoma while making it more susceptible to conventional therapy. Noncoding RNA, 2019, 5(1), 25.
[23]
Paolone, G.; Falcicchia, C.; Lovisari, F. Long-term, targeted delivery of GDNF from encapsulated cells is neuroprotective and reduces seizures in the pilocarpine model of epilepsy. J. Neurosci., 2019, 39(11), 2144-2156.
[http://dx.doi.org/10.1523/JNEUROSCI.0435-18.2018] [PMID: 30665947]
[24]
Yoo, Y-M.; Lee, C-J.; Lee, U.; Kim, Y.J. Neuroprotection of adenoviral-vector-mediated GDNF expression against kainic-acid-induced excitotoxicity in the rat hippocampus. Exp. Neurol., 2006, 200(2), 407-417.
[http://dx.doi.org/10.1016/j.expneurol.2006.02.132] [PMID: 16690057]

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