Effect of miR-124 on PI3K/Akt signal pathway in refractory epilepsy rats

Ruili Wang; Xuelin An; Shuzhi Zhao

doi:10.14715/cmb/2020.66.2.24

Issue

Vol. 66 No. 2: Issue 2

Issue Published : May 16, 2020

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Effect of miR-124 on PI3K/Akt signal pathway in refractory epilepsy rats

https://doi.org/10.14715/cmb/2020.66.2.24

Ruili Wang

Department of Neurology, Liaocheng Third People‘s Hospital, Liaocheng 252000, P.R. China

Xuelin An

Department of Neurology, Liaocheng Third People‘s Hospital, Liaocheng 252000, P.R. China

Shuzhi Zhao

Department of Neurology, Liaocheng Third People‘s Hospital, Liaocheng 252000, P.R. China

Corresponding Author(s) : Ruili Wang

wang123shi@gmail.com

Cellular and Molecular Biology, Vol. 66 No. 2: Issue 2
Article Published : May 15, 2020

Abstract

This research aimed to investigate the effect of miR-124 on the PI3K/Akt signaling pathway in refractory epilepsy rats. Ten healthy SD rats were selected as a control group, thirty-six successfully established model rats were randomly divided into the model group, mir-124-agomir, mir-124-antagomir, mir-124-agomir+ LY294002 group (combined group), with 9 rats in each group. PI3K or (and) Akt expressions were intervened respectively. The changes in attack latency and cognitive function were observed, and the correlation among miR-124, PI3K, Akt, and attack latency was analyzed. Up-regulation of the level of miR-124 could increase the seizure interval of rats (P< 0.05), improve the cognitive function of rats (P< 0.05), and promote the expression of PI3K, AKT. The level of miR-124, PI3K, Akt was positively correlated with the latent time of seizures in rats, and the level of miR-124 was positively correlated with the level of PI3K, Akt (P< 0.05). In conclusion, miR-124 can play a protective role in temporal lobe epilepsy by promoting PI3K/Akt signaling pathway, including the protection of cognitive function, which may be a potential target for clinical treatment of intractable epilepsy in the future.

Keywords

miR-124 Refractory epilepsy Rats PI3K/Akt Signal Pathway

Wang, R., An, X., & Zhao, S. (2020). Effect of miR-124 on PI3K/Akt signal pathway in refractory epilepsy rats. Cellular and Molecular Biology, 66(2), 146–152. https://doi.org/10.14715/cmb/2020.66.2.24

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References

Winawer MR, Griffin NG, Samanamud J, Baugh EH, Ra¬thakrishnan D, Ramalingam S, Zagzag D, Schevon CA, Dugan P, Hegde M, A. Sheth S, M. McKhann G, K. Doyle W, A. Grant G, E. Porter B, A. Mikati M, R. Muh C, D. Malone C, R. Bergin AM, M. Peters J, K. McBrian D, M. Pack A, I. Akman C, M. LaCoursiere C, M. Keever K, R. Madsen J, Yang E, Lidov HGW, Shain C, S. Allen A, Canoll P, B. Crino P, H. Poduri A, L. Heinzen E. Somatic SLC35A2 variants in the brain are associated with intractable neo¬cortical epilepsy. Ann Neurol 2018; 83: 1133-1146.
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Mohanraj R, Brodie MJ. Diagnosing refractory epilepsy: res¬ponse to sequential treatment schedules. Eur J Neurol 2006; 13: 277-282.
Tzadok M, Uliel-Siboni S, Linder I, Kramer U, Epstein O, Menascu S, Nissenkorn A, Yosef OB, Hyman E, Granot D, Dor M, Lerman-Sagie T, Ben-Zeev B. CBD-enriched medical cannabis for intractable pediatric epilepsy: the current Israeli experience. Seizure 2016; 35: 41-44.
Lou Y, Shi J, Guo D, Qureshi AK, Song L. Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Biol Sci 2017; 24(4): 803-807.
Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L, Luo F. Octacosa¬nol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 65(18): 3647-3658, 2017.
Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX, Liu C. As¬sociation of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 9(3): 107-119, 2019.
Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T, Lin Q. Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 8(11): 4028- 4041, 2017.
Lou Y, Yang J, Wang L, Chen X, Xin X, Liu Y. The clinical efficacy study of treatment to Chiari malformation type I with sy¬ringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 26(8): 1927-1931, 2019.
Englot DJ, Raygor KP, Molinaro AM, Garcia PA, Knowlton RC, Auguste KI, Chang EF. Factors associated with failed focal neocor¬tical epilepsy surgery. Neurosurgery 2014; 75: 648-656.
Englot DJ, Rolston JD, Wright CW, Hassnain KH, Chang EF. Rates and predictors of seizure freedom with vagus nerve stimula¬tion for intractable epilepsy. Neurosurgery 2015; 79: 345-353.
Yen CS, Su ZR, Lee YP, Liu IT, Yen CJ. miR-106b promotes cancer progression in hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol 2016; 22: 5183-5192.
McKiernan RC, Jimenez-Mateos EM, Bray I, Engel T, Brennan GP, Sano T, Michalak Z, Moran C, Delanty N, Farrell M, O'Brien D, Meller R, P. Simon R, L. Stallings R, C. Henshall D. Reduced mature microRNA levels in association with dicer loss in human temporal lobe epilepsy with hippocampal sclerosis. PLoS One 2012; 7: e35921.
Peng J, Omran A, Ashhab MU, Kong H, Gan N, He F, Yin F. 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.
Reschke CR, Silva LF, Norwood BA, Senthilkumar K, Morris G, Sanz-Rodriguez A, Conroy RM, Costard L, Neubert V, Bauer S, A.Farrell M, F.O'Brien D, Delanty N, Schorge S, Pasterkamp RJ, Rosenow F, C.Henshall D. Potent anti-seizure effects of locked nucleic acid antagomirs targeting miR-134 in multiple mouse and rat models of epilepsy. Mol Ther Nucleic Acids 2017; 6: 45-56.
Wang XM, Jia RH, Wei D, Cui WY, Jiang W. MiR-134 bloc¬kade prevents status epilepticus like-activity and is neuroprotective in cultured hippocampal neurons. Neurosci Lett 2014; 572: 20-25.
Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F. Oryza¬nol modifies high fat diet-induced obesity, liver gene expression pro¬file, and inflammation response in mice. J Agri Food Chem 65(38): 8374-8385, 2017.
Lou Y, Guo D, Zhang H and Song L: Effectiveness of mesenchy¬mal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 11(1): 519-523, 2016.
Chen X, Xu Y, Meng L, Chen X, Yuan L, Cai Q, Shi W and Huang G. Non-parametric partial least squares–discriminant analy¬sis model based on sum of ranking difference algorithm for tea grade identification using electronic tongue data identify tea grade using e-tongue data. Sens Actuators B Chem 127924, 2020.
Nie Y, Luo F and Lin Q. Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 75: 72-80, 2018.
Ren Y, Jiao X and Zhang L. Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci 25(3): 469-473, 2018.
Wang W, Wang X, Chen L, Wang W, Wang X, Chen L, Zhang Y, Xu Z, Liu J, Jiang G, Li J, Zhang X, Wang K, Wang J, Chen G, Luo J. The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity. Expert reviews in molecular medicine, 2016; 18.
Levesque M, Avoli M, Bernard C. Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration. J Neurosci Methods 2016; 260: 45-52.
Shao Y, Wang C, Hong Z, Chen Y. Inhibition of p38 mitogen"activated protein kinase signaling reduces multidrug transporter activity and anti"epileptic drug resistance in refractory epileptic rats. J Neurochem 2016; 136: 1096-1105.
Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J. Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-ÎºB Signaling. J Agri Food Chem 66(2): 440-448, 2018.
Gu X, Meng S, Liu S, Jia C, Fang Y, Li S, Fu C, Song Q, Lin L, Wang X. miR-124 represses ROCK1 expression to promote neurite elongation through activation of the PI3K/Akt signal pathway. J Mol Neurosci 2014; 52(1): 156-165.
Wang C, Wei Z, Jiang G, Liu H. Neuroprotective mechanisms of miR-124 activating PI3K/Akt signaling pathway in ischemic stroke. Exp Ther Med 2017; 13: 3315-3318.
Henshall DC, Hamer HM, Pasterkamp RJ, Goldstein DB, Kjems J, Prehn JHM, Schorge S, Lamottke K, Rosenow F. MicroRNAs in epilepsy: pathophysiology and clinical utility. Lancet Neurol 2016; 15: 1368-1376.
Berdichevsky Y, Dryer AM, Saponjian Y, Mahoney MM, Pi¬mentel CA, Lucini CA, Usenovic M, Staley KJ. PI3K-Akt signaling activates mTOR-mediated epileptogenesis in organotypic hippo¬campal culture model of posttraumatic epilepsy. J Neurosci 2013; 33: 9056-9067.
Xiao Z, Peng J, Yang L, Kong H, Yin F. Interleukin-1Î² plays a role in the pathogenesis of mesial temporal lobe epilepsy through the PI3K/Akt/mTOR signaling pathway in hippocampal neurons. J Neuroimmunol 2015; 282: 110-117.
Wang SW, Deng LX, Chen HY, Su ZQ, Ye SL, Xu WY. MiR- 124 affects the apoptosis of brain vascular endothelial cells and ROS production through regulating PI3K/AKT signaling pathway. Eur Rev Med Pharmacol Sci 2018; 22: 498-505.
Kang Q, Xiang Y, Li D, Liang J, Zhang X, Zhou F, Qiao M, Nie Y, He Y, Cheng J, Dai Y, Li Y. MiR-124-3p attenuates hyperphos¬phorylation of Tau protein- induced apoptosis via caveolin-1-PI3K/ Akt/GSK3Î² pathway in N2a/APP695swe cells. Oncotarget 2017; 8: 24314-24326.
Manna I, Labate A, Borzí¬ G, Mumoli L, Cavalli SM, Sturniolo M, Quattrone A, Gambardella A. An SNP site in pri-miR-124, a brain expressed miRNA gene, no contribution to mesial temporal lobe epilepsy in an Italian sample. Neurol Sci 2016; 37: 1335-1339.
Brennan GP, Dey D, Chen Y, Patterson KP, Magnetta EJ, Hall AM, Dube CM, Mei YT, Baram TZ. Dual and opposing roles of microRNA-124 in epilepsy are mediated through inflammatory and NRSF-dependent gene networks. Cell Rep 2016; 14: 2402-2412.

References

Winawer MR, Griffin NG, Samanamud J, Baugh EH, Ra¬thakrishnan D, Ramalingam S, Zagzag D, Schevon CA, Dugan P, Hegde M, A. Sheth S, M. McKhann G, K. Doyle W, A. Grant G, E. Porter B, A. Mikati M, R. Muh C, D. Malone C, R. Bergin AM, M. Peters J, K. McBrian D, M. Pack A, I. Akman C, M. LaCoursiere C, M. Keever K, R. Madsen J, Yang E, Lidov HGW, Shain C, S. Allen A, Canoll P, B. Crino P, H. Poduri A, L. Heinzen E. Somatic SLC35A2 variants in the brain are associated with intractable neo¬cortical epilepsy. Ann Neurol 2018; 83: 1133-1146.

Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshé SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010; 51: 1069-1077.

Mohanraj R, Brodie MJ. Diagnosing refractory epilepsy: res¬ponse to sequential treatment schedules. Eur J Neurol 2006; 13: 277-282.

Tzadok M, Uliel-Siboni S, Linder I, Kramer U, Epstein O, Menascu S, Nissenkorn A, Yosef OB, Hyman E, Granot D, Dor M, Lerman-Sagie T, Ben-Zeev B. CBD-enriched medical cannabis for intractable pediatric epilepsy: the current Israeli experience. Seizure 2016; 35: 41-44.

Lou Y, Shi J, Guo D, Qureshi AK, Song L. Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Biol Sci 2017; 24(4): 803-807.

Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L, Luo F. Octacosa¬nol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 65(18): 3647-3658, 2017.

Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX, Liu C. As¬sociation of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 9(3): 107-119, 2019.

Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T, Lin Q. Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 8(11): 4028- 4041, 2017.

Lou Y, Yang J, Wang L, Chen X, Xin X, Liu Y. The clinical efficacy study of treatment to Chiari malformation type I with sy¬ringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 26(8): 1927-1931, 2019.

Englot DJ, Raygor KP, Molinaro AM, Garcia PA, Knowlton RC, Auguste KI, Chang EF. Factors associated with failed focal neocor¬tical epilepsy surgery. Neurosurgery 2014; 75: 648-656.

Englot DJ, Rolston JD, Wright CW, Hassnain KH, Chang EF. Rates and predictors of seizure freedom with vagus nerve stimula¬tion for intractable epilepsy. Neurosurgery 2015; 79: 345-353.

Yen CS, Su ZR, Lee YP, Liu IT, Yen CJ. miR-106b promotes cancer progression in hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol 2016; 22: 5183-5192.

McKiernan RC, Jimenez-Mateos EM, Bray I, Engel T, Brennan GP, Sano T, Michalak Z, Moran C, Delanty N, Farrell M, O'Brien D, Meller R, P. Simon R, L. Stallings R, C. Henshall D. Reduced mature microRNA levels in association with dicer loss in human temporal lobe epilepsy with hippocampal sclerosis. PLoS One 2012; 7: e35921.

Peng J, Omran A, Ashhab MU, Kong H, Gan N, He F, Yin F. 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.

Reschke CR, Silva LF, Norwood BA, Senthilkumar K, Morris G, Sanz-Rodriguez A, Conroy RM, Costard L, Neubert V, Bauer S, A.Farrell M, F.O'Brien D, Delanty N, Schorge S, Pasterkamp RJ, Rosenow F, C.Henshall D. Potent anti-seizure effects of locked nucleic acid antagomirs targeting miR-134 in multiple mouse and rat models of epilepsy. Mol Ther Nucleic Acids 2017; 6: 45-56.

Wang XM, Jia RH, Wei D, Cui WY, Jiang W. MiR-134 bloc¬kade prevents status epilepticus like-activity and is neuroprotective in cultured hippocampal neurons. Neurosci Lett 2014; 572: 20-25.

Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F. Oryza¬nol modifies high fat diet-induced obesity, liver gene expression pro¬file, and inflammation response in mice. J Agri Food Chem 65(38): 8374-8385, 2017.

Lou Y, Guo D, Zhang H and Song L: Effectiveness of mesenchy¬mal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 11(1): 519-523, 2016.

Chen X, Xu Y, Meng L, Chen X, Yuan L, Cai Q, Shi W and Huang G. Non-parametric partial least squares–discriminant analy¬sis model based on sum of ranking difference algorithm for tea grade identification using electronic tongue data identify tea grade using e-tongue data. Sens Actuators B Chem 127924, 2020.

Nie Y, Luo F and Lin Q. Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 75: 72-80, 2018.

Ren Y, Jiao X and Zhang L. Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci 25(3): 469-473, 2018.

Wang W, Wang X, Chen L, Wang W, Wang X, Chen L, Zhang Y, Xu Z, Liu J, Jiang G, Li J, Zhang X, Wang K, Wang J, Chen G, Luo J. The microRNA miR-124 suppresses seizure activity and regulates CREB1 activity. Expert reviews in molecular medicine, 2016; 18.

Levesque M, Avoli M, Bernard C. Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration. J Neurosci Methods 2016; 260: 45-52.

Shao Y, Wang C, Hong Z, Chen Y. Inhibition of p38 mitogen"activated protein kinase signaling reduces multidrug transporter activity and anti"epileptic drug resistance in refractory epileptic rats. J Neurochem 2016; 136: 1096-1105.

Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J. Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-ÎºB Signaling. J Agri Food Chem 66(2): 440-448, 2018.

Gu X, Meng S, Liu S, Jia C, Fang Y, Li S, Fu C, Song Q, Lin L, Wang X. miR-124 represses ROCK1 expression to promote neurite elongation through activation of the PI3K/Akt signal pathway. J Mol Neurosci 2014; 52(1): 156-165.

Wang C, Wei Z, Jiang G, Liu H. Neuroprotective mechanisms of miR-124 activating PI3K/Akt signaling pathway in ischemic stroke. Exp Ther Med 2017; 13: 3315-3318.

Henshall DC, Hamer HM, Pasterkamp RJ, Goldstein DB, Kjems J, Prehn JHM, Schorge S, Lamottke K, Rosenow F. MicroRNAs in epilepsy: pathophysiology and clinical utility. Lancet Neurol 2016; 15: 1368-1376.

Berdichevsky Y, Dryer AM, Saponjian Y, Mahoney MM, Pi¬mentel CA, Lucini CA, Usenovic M, Staley KJ. PI3K-Akt signaling activates mTOR-mediated epileptogenesis in organotypic hippo¬campal culture model of posttraumatic epilepsy. J Neurosci 2013; 33: 9056-9067.

Xiao Z, Peng J, Yang L, Kong H, Yin F. Interleukin-1Î² plays a role in the pathogenesis of mesial temporal lobe epilepsy through the PI3K/Akt/mTOR signaling pathway in hippocampal neurons. J Neuroimmunol 2015; 282: 110-117.

Wang SW, Deng LX, Chen HY, Su ZQ, Ye SL, Xu WY. MiR- 124 affects the apoptosis of brain vascular endothelial cells and ROS production through regulating PI3K/AKT signaling pathway. Eur Rev Med Pharmacol Sci 2018; 22: 498-505.

Kang Q, Xiang Y, Li D, Liang J, Zhang X, Zhou F, Qiao M, Nie Y, He Y, Cheng J, Dai Y, Li Y. MiR-124-3p attenuates hyperphos¬phorylation of Tau protein- induced apoptosis via caveolin-1-PI3K/ Akt/GSK3Î² pathway in N2a/APP695swe cells. Oncotarget 2017; 8: 24314-24326.

Manna I, Labate A, Borzí¬ G, Mumoli L, Cavalli SM, Sturniolo M, Quattrone A, Gambardella A. An SNP site in pri-miR-124, a brain expressed miRNA gene, no contribution to mesial temporal lobe epilepsy in an Italian sample. Neurol Sci 2016; 37: 1335-1339.

Brennan GP, Dey D, Chen Y, Patterson KP, Magnetta EJ, Hall AM, Dube CM, Mei YT, Baram TZ. Dual and opposing roles of microRNA-124 in epilepsy are mediated through inflammatory and NRSF-dependent gene networks. Cell Rep 2016; 14: 2402-2412.

Author biographies is not available.