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Vol. 65 No. 2: Issue 2

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Expression of Nav1.5 in the pathogenesis of temporal lobe epilepsy

https://doi.org/10.14715/cmb/2019.65.2.9
Yi Zhou
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
Zhaohui Luo
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
Fangfang Bi
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
Jing Li
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
Bo Xiao
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China

Corresponding Author(s) : Bo Xiao

xiaobo_xy@126.com

Cellular and Molecular Biology, Vol. 65 No. 2: Issue 2

Abstract

To investigate the expressions of Nav1.5 mRNA at different time points in a rat model of temporal lobe epilepsy (TLE), and to assess the potential contribution of Nav1.5 to epileptogenesis. Male Sprague-Dawley rats (72) weighing 230 to 250 g were used for this study. They were randomly assigned to six groups (12 rats/group): control and five TLE groups. The TLE groups were day 1 (acute period), days 7 and 14 (latent period), and days 30 and 60 (chronic period). With the exception of control, epilepsy was induced in the rats with an intraperitoneal (i.p.) injection of aqueous solution of lithium chloride 18 h prior to pilocarpine injection (i.p.) at a dose of 125 mg/kg body weight (b.wt). Rats in the control group were injected i.p. with 0.9 % sodium chloride (125 mg/kg b.wt.) in place of pilocarpine. A total of 84 out of 112 rats developed status epilepticus (SE). The expression of Nav1.5 in the brains of rats was assessed using quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry and Western blot analysis. The expressions of Scn5a mRNA in the hippocampus during the latent and chronic periods were significantly higher than in the control group (p < 0.05), but there were no significant differences in the corresponding expressions between the two different time points in the latent and chronic period groups (p > 0.05). The expression peaked 30 days post-SE, and was sustained for 60 days. There was no significant difference in the expression of Scn5a mRNA in the acute group, when compared to control. Immunohistochemical staining showed that expression levels of Nav1.5 in the CA3 region during latent and chronic periods were significantly higher than those in control group (p < 0.05), and the expressions peaked at day 30. However, there was no significant difference in the expression of Nav1.5 in the latent group, relative to the chronic period group. These results show that Nav1.5 might be involved in the pathogenesis of TLE.

Keywords

Temporal lobe epilepsy Voltage-gated sodium channel Hippocampus Seizures Expression.
Zhou, Y., Luo, Z., Bi, F., Li, J., & Xiao, B. (2019). Expression of Nav1.5 in the pathogenesis of temporal lobe epilepsy. Cellular and Molecular Biology, 65(2), 58–62. https://doi.org/10.14715/cmb/2019.65.2.9
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References
  1. Berg AT. Defining intractable epilepsy. Adv Neurol 2006; 97: 5-10.
  2. Pitkanen A, Sutula TP. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lamcet Neurol 2002; 1: 173 - 181.
  3. Waxman SG. The neuron as a dynamic electrogenic machine: modulation of sodium-channel expression as a basis for functional plasticity in neurons. Lamcet Neurol 2000; 355: 199-213.
  4. Stafstrom CE. Persistent sodium current and its role in epilepsy. Epilepsy Curr 2007; 7: 15-22.
  5. Catterall WA. Sodium channels, inherited epilepsy, and antiepileptic drugs. Annu Rev Pharmacol Toxicol 2014; 54: 317-338.
  6. Meisler MH, Kearney JA. Sodium channel mutations in epilepsy and other neurological disorders. J Clin Invest 2005; 115: 2010-2017.
  7. Guo F, Yu N, Cai JQ. Voltage-gated sodium channel Nav1.1, Nav1.3 and beta1 subunit were up-regulated in the hippocampus of spontaneously epileptic rat. Brain Res Bull 2008; 75: 179-187.
  8. Chen X, Johnston D. Voltage-gated ion channels in dendrites of hippocampal pyramidal neurons. Pflugers Arch 2006; 453: 397-401.
  9. Blumenfeld H, Lampert A, Klein JP, Mission J, Chen MC, Rivera M, et al. Role of hippocampal sodium channel Nav1.6 in kindling epileptogenesis. Epilepsia 2009; 50: 44-55.
  10. Catterall WA, Kalume F, Oakley JC. NaV1.1 channels and epilepsy. J Physiol 2010; 588: 1849-1859.
  11. Donahue LM, Coates PW, Lee VH, Ippensen DC, Arze SE, Poduslo SE. The cardiac sodium channel mRNA is expressed in the developing and adult rat and human brain. Brain Res 2000; 887: 335-343.
  12. Gersdorff-Korsgaard MP, Christophersen P, Ahring PK, Olesen SP. Identification of a novel voltage-gated Na+ channel rNa (v) 1.5a in the rat hippocampal progenitor stem cell line HiB5. Pflugers Arch 2001; 443: 18-30.
  13. Aurlien D, Leren TP, Tauboll E, Gjerstad L. New SCN5A mutation in a SUDEP victim with idiopathic epilepsy. Seizure 2009; 18: 158-160.
  14. World Health Organization. Principles of laboratory animal care. WHO Chron 1985; 39: 51-56.
  15. Wallace RH, Wang DW, Singh R, Scheffer IE, George AL Jr, Phillips HA, et al. Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet 1998; 19: 366-370.
  16. Gambardella A, Marini C. Clinical spectrum of SCN1A mutations. Epilepsia 2009; 50: 20-23.
  17. Shi X, Yasumoto S, Kurahashi H, Nakagawa E, Fukasawa T, Uchiya S, et al. Clinical spectrum of SCN2A mutations. Brain Dev 2012; 34: 541-545.
  18. Klein JP, Khera DS, Nersesyan H, Kimchi EY, Waxman SG, Blumenfeld H. Dysregulation of sodium channel expression in cortical neurons in a rodent model of absence epilepsy. Brain Res 2004; 1000: 102-109.
  19. Dulong C, Fang YJ, Gest C, Zhou MH, Patte-Mensah C, Mensah-Nyagan AG, et al. The small GTPase RhoA regulates the expression and function of the sodium channel Nav1.5 in breast cancer cells. Int J Oncol 2014; 44: 539-547.
  20. Parisi P, Oliva A, Coll-Vidal M, Partemi S, Campuzano O, Iglesias A, et al. Coexistence of epilepsy and Brugada syndrome in a family with SCN5A mutation. Epilepsy Res 2013; 105: 415-418.
  21. Nicholson E, Randall AD. Na(v)1.5 sodium channels in a human microglial cell line. J Neuroimmunol 2009; 215: 25-30.
  22. Vezzani A, Ravizza T, Balosso S, Aronica E. Glia as a source of cytokines: implications for neuronal excitability and survival. Epilepsia 2008; 49: 24-32.
  23. Mercier A, Clement R, Harnois T, Bourmeyster N, Bois P, Chatelier A. Na1.5 channels can reach the plasma membrane through distinct N-glycosylation states. Biochim Biophys Acta 2015; 1850: 1215-1223.
  24. Han Z, Jiang Y, Xiao F, Cao K, Wang DW. The effects of A-803467 on cardiac Na1.5 channels. Eur J Pharmacol 2015; 754: 52-60.
  25. Hund TJ, Koval OM, Li J, Wright PJ, Qian L, Snyder JS, et al. A beta (IV)-spectrin/CaMKII signaling complex is essential for membrane excitability in mice. J Clin Invest 2010; 120: 3508-3519.
  26. Jensen HS, Grunnet M, Bastlund JF. Therapeutic potential of Na (V)1.1 activators. Trends Pharmacol Sci 2014; 35: 113-118.
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