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http://dx.doi.org/10.5352/JLS.2020.30.6.513

The Role of Bmi1 in Pilocarpine-induced Status Epilepticus in Mice  

Pyeon, Hae-In (Department of Pharmacy, Kyungsung University)
Bak, Jia (Department of Pharmacy, Kyungsung University)
Choi, Yun-Sik (Department of Pharmacy, Kyungsung University)
Publication Information
Journal of Life Science / v.30, no.6, 2020 , pp. 513-521 More about this Journal
Abstract
B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) is a polycomb group protein and a core component of polycomb repressive complex 1. Initial research into Bmi1 has focused on its role in tumorigenesis, and it is generally accepted that it is important for the proliferation and survival of cancer cells. However, more recent studies have revealed that Bmi1 is downregulated in brains with neurodegenerative disease and that it regulates the function of mitochondria and reactive oxygen species levels. In this study, we tested the therapeutic potential of Bmi1 in pilocarpine-induced seizures in Bmi1-knockout mice. Bmi1 expression transiently increased in the hippocampal CA1 and CA3 and the dentate gyrus following pilocarpine-induced status epilepticus (SE). In terms of seizure behavior, SE induction was 43.14% and 53.57% for Bmi1+/+ and Bmi1+/- mice, respectively. However, there was no significant difference in mortality or hippocampal damage between the two groups. Two months after SE induction, the frequency of epileptic seizures in the Bmi1+/- mice was 50% lower than in the control group, although the difference was not statistically significant. In addition, mossy fiber outgrowth in the Bmi1+/- mice was significantly higher than in their wild-type littermates. Taken together, these data indicate that reduced Bmi1 activity increases pilocarpine-induced seizure probability and mossy fiber outgrowth.
Keywords
Bmi1; mossy fiber sprouting; pilocarpine; recurrent seizure; status epilepticus;
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1 Janaki Ramaiah, M. and Vaishnave, S. 2018. BMI1 and PTEN are key determinants of breast cancer therapy: A plausible therapeutic target in breast cancer. Gene 678, 302-311.   DOI
2 Katzung, B. G. 2018. Basic & Clinical Pharmacology, pp. 409, 14th ed., McGraw-Hill: 1325 Avenue of the Americas New York, NY, USA.
3 Lee, K. E., Cho, K. O., Choi, Y. S. and Kim, S. Y. 2016. The neuroprotective mechanism of ampicillin in a mouse model of transient forebrain ischemia. Kor. J. Physiol. Pharmacol. 20, 185-192.   DOI
4 Leung, C., Lingbeek, M., Shakhova, O., Liu, J., Tanger, E., Saremaslani, P., Van Lohuizen, M. and Marino, S. 2004. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 428, 337-341.   DOI
5 Li, A., Choi, Y. S., Dziema, H., Cao, R., Cho, H. Y., Jung, Y. J. and Obretan, K. 2010. Proteomic profiling of the epileptic dentate gyrus. Brain Pathol. 20, 1077-1089.   DOI
6 Li, J., Vangundy, Z. and Poi, M. 2020. PTC209, a specific inhibitor of BMI1, promotes cell cycle arrest and apoptosis in cervical cancer cell lines. Anticancer Res. 40, 133-141.   DOI
7 Liu. J., Cao, L., Chen, J., Song, S., Lee, I. H., Quijano, C., Liu, H., Keyvanfar, K., Chen, H., Cao, L. Y., Ahn, B. H., Kumar, N. G., Rovira, I. I., Xu, X. L., Van Lohuizen, M., Motoyama, N., Deng, C. X. and Finkel, T. 2009. Bmi1 regulates mitochondrial function and the DNA damage response pathway. Nature 459, 387-392.   DOI
8 Masukawa, L. M., Uruno, K., Sperling, M., O'Connor, M. J. and Burdette, L. J. 1992. The functional relationship between antidromically evoked field responses of the dentate gyrus and mossy fiber reorganization in temporal lobe epileptic patients. Brain Res. 579, 119-127.   DOI
9 Park, I. K., Morrison, S. J. and Clarke, M. F. 2004. Bmi1, stem cells, and senescence regulation. J. Clin. Invest. 113, 175-179.   DOI
10 Pathan, S. A., Jain, G. K., Akhter, S., Vohora, D., Ahmad, F. J. and Khar, R. K. 2010. Insights into the novel three 'D's of epilepsy treatment: drugs, delivery systems and devices. Drug Discov. Today 15, 717-732.   DOI
11 Polli, R. S., Malheirosm, J. M., Dos Santos, R., Hamani, C., Longo, B. M., Tannús, A., Mello, L. E. and Covolan, L. 2014. Changes in hippocampal volume are correlated with cell loss but not with seizure frequency in two chronic models of temporal lobe epilepsy. Front Neurol. 5, 111.
12 Racine, R. J. 1972. Modification of seizure activity by electrical stimulation. II. motor seizure. Electroencephalogr. Clin. Neurophysiol. 32, 281-294.   DOI
13 Represa, A., Jorquera, I., Le Gal La Salle, G. and Ben-Ari, Y. 1993. Epilepsy induced collateral sprouting of hippocampal mossy fibers: does it induce the development of ectopic synapses with granule cell dendrites? Hippocampus 3, 257-268.
14 Shibley, H. and Smith, B. N. 2002. Pilocarpine-induced status epilepticus results in mossy fiber sprouting and spontaneous seizures in C57BL/6 and CD-1 mice. Epilepsy Res. 49, 109-120.   DOI
15 Reynolds, J. P., Miller-Delaney, S. F., Jimenez-Mateos, E. M., Sano, T., McKiernan, R. C., Simon, R. P. and Henshall, D. C. 2015. Transcriptional response of polycomb group genes to status epilepticus in mice is modified by prior exposure to epileptic preconditioning. Front Neurol. 6, 46.   DOI
16 Schmeiser, B., Zentner, J., Prinz, M., Brandt, A. and Freiman, T. M. 2017. Extent of mossy fiber sprouting in patients with mesiotemporal lobe epilepsy correlates with neuronal cell loss and granule cell dispersion. Epilepsy Res. 129, 51-58.   DOI
17 Schmidt, D. 2009. Drug treatment of epilepsy: options and limitations. Epilepsy Behav. 15, 56-65.   DOI
18 Valk-Lingbeek, M. E., Bruggeman, S. W. and van Lohuizen,M. 2004. Stem cells and cancer; the polycomb connection.Cell 118, 409-418.   DOI
19 Stapels, M., Piper, C., Yang, T., Li, M., Stowell, C., Xiong, Z. G., Saugstad, J., Simon, R. P., Geromanos, S., Langridge, J., Lan, J. Q. and Zhou, A. 2010. Polycomb group proteins as epigenetic mediators of neuroprotection in ischemictolerance. Sci. Signal. 3, 10.
20 Trahair, T. N., Liu, T., Wainwright, B. J., Ding, H. F. andMarshall, G. M. 2013. Direct effects of Bmi1 on p53 proteinstability inactivates oncoprotein stress responses in embryonalcancer precursor cells at tumor initiation. Oncogene 32,3616-3626.   DOI
21 Wang, M. C., Li, C. L., Cui, J., Jiao, M., Wu, T., Jing, L.and Nan, K. J. 2015. BMI-1, a promising therapeutic targetfor human cancer. Oncol. Lett. 10, 583-588.   DOI
22 Cavarsan, C. F., Malheiros, J., Hamani, C., Najm, I. and Covolan, L. 2018. Is mossy fiber sprouting a potential therapeutic target for epilepsy? Front Neurol. 9, 1023.   DOI
23 Xu, X., Wang, Z., Liu, N., Zhang, P., Liu, H., Qi, J. andTu, Y. 2018. The mechanism of BMI1 in regulating cancerstemness maintenance, metastasis, chemo- and radiationresistance. Cancer Transl. Med. 4, 59-63.   DOI
24 Siddique, H. R. and Saleem, M. 2012. Role of BMI1, a stem cell factor, in cancer recurrence and chemoresistance: preclinical and clinical evidences. Stem Cells 30, 372-378.   DOI
25 Abdouh, M., Chatoo, W., El, H. J., David, J., Ferreira, J. and Bernier, G. 2012. Bmi1 is down-regulated in the aging brain and displays antioxidant and protective activities in neurons. PLoS One 7, e31870.   DOI
26 Barabino, A., Plamondon, V., Abdouh, M., Chatoo, W., Flamier, A., Hanna, R., Zhou, S., Motoyama, N., Hebert, M., Lavoie, J. and Bernier, G. 2016. Loss of Bmi1 causes anomalies in retinal development and degeneration of cone photoreceptors. Development 143, 1571-1584.   DOI
27 Calao, M., Sekyere, E. O., Cui, H. J., Cheung, B. B., Thomas, W. D., Keating, J., Chen, J. B., Raif, A., Jankowski, K., Davies, N. P., Bekkum, M. V., Chen, B., Tan, O., Ellis, T., Norris, M. D., Haber, M., Kim, E. S., Shohet, J. M., Trahair, T. N., Liu, T., Wainwright, B. J., Ding, H. F. and Marshall, G. M. 2013. Direct effects of Bmi1 on p53 protein stability inactivates oncoprotein stress responses in embryonal cancer precursor cells at tumor initiation. Oncogene 32, 3616-3626.   DOI
28 Chatoo, W., Abdouh, M., David, J., Champagne, M. P., Ferreira, J., Rodier, F. and Bernier, G. 2009. The polycomb group gene Bmi1 regulates antioxidant defenses in neurons by repressing p53 pro-oxidant activity. J. Neurosci. 29, 529-542.   DOI
29 Courel, M., Friesenhahn, L. and Lees, J. A. 2008. E2f6 and Bmi1 cooperate in axial skeletal development. Dev. Dyn. 237, 1232-1242.   DOI
30 Chen, Z., Brodie, M. J., Liew, D. and Kwan, P. 2018. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 75, 279-286.   DOI
31 Davies, J. A. 1995. Mechanisms of action of antiepileptic drugs. Seizure 4, 267-271.   DOI
32 El Hajjar, J., Chatoo, W., Hanna, R., Nkanza, P., Tétreault, N., Tse, Y. C., Wong, T. P., Abdouh, M. and Bernier, G. 2019. Heterochromatic genome instability and neurodegeneration sharing similarities with Alzheimer's disease in old Bmi1+/- mice. Sci. Rep. 9, 594.   DOI
33 de Lanerolle, N. C., Kim, J. H., Williamson, A., Spencer, S. S., Zaveri, H. P., Eid, T. and Spencer, D. D. 2003. A retrospective analysis of hippocampal pathology in human temporal lobe epilepsy: evidence for distinctive patient subcategories. Epilepsia 44, 677-687.   DOI
34 Dey, A., Xiong, X., Crim, A., Dwivedi, S. K. D., Mustafi, S. B., Mukherjee, P., Cao, L., Sydorenko, N., Baiazitov, R., Moon, Y. C., Dumble, M., Davis, T. and Bhattacharya, R. 2018. Evaluating the mechanism and therapeutic potential of PTC-028, a novel inhibitor of BMI-1 function in ovarian cancer. Mol. Cancer Ther. 17, 39-49.   DOI
35 Ding, X., Lin, Q., Ensenat-Waser, R., Rose-John, S. and Zenke, M. 2012. Polycomb group protein Bmi1 promotes hematopoietic cell development from embryonic stem cells. Stem Cells Dev. 21, 121-132.   DOI
36 Heng, K., Haney, M. M. and Buckmaster, P. S. 2013. Highdose rapamycin blocks mossy fiber sprouting but not seizures in a mouse model of temporal lobe epilepsy. Epilepsia 54, 1535-1541.   DOI
37 Ginjala, V., Nacerddine, K., Kulkarni, A., Oza, J., Hill, S. J., Yao, M., Citterio, E., van Lohuizen, M. and Ganesan, S. 2011. Bmi1 is recruited to DNA breaks and contributes to DNA damage-induced H2A ubiquitination and repair. Mol. Cell Biol. 31, 1972-1982.   DOI
38 Gu, M., Shen, L., Bai, L., Gao, J., Marshall, C., Wu, T., Ding, J., Miao, D. and Xiao, M. 2014. Heterozygous knockout of the Bmi-1 gene causes an early onset of phenotypes associated with brain aging. Age (Dordr) 36, 129-139.   DOI