Araştırma Makalesi
Yıl 2020,
Cilt: 45 Sayı: 4, 1580 - 1586, 27.12.2020
Öz
Purpose: Status epilepticus (SE) is a highly common neurological disease in children, with recurrent generalized convulsions for more than 30 minutes, and when not controlled, neuronal damage occurs in the brain. The aim of this study was to evaluate the changes in KCNQ1 and KCNQ3 gene expression levels in the acute period after SE.
Materials and Methods: In rats, an experimental SE model was created with Li-Pc. Study; female Wistar albino [250–350 g, 21 (n=7)] rats were used in 3 groups as SE, control and sham groups. The total RNA obtained from brain tissues was converted to cDNA, and gene expression levels of KCNQ1 and KCNQ3 genes were assessed by quantitative real-time PCR (qRT-PCR) method.
Results: Statistically in SE group; compared to the control and sham groups, a significant difference was observed in the gene expression levels of the KCNQ1 and KCNQ3 ion channels. The KCNQ1 and KCNQ3 gene expression levels of the experimental group was found higher than the other groups.
Conclusion: Determining the changes in mRNA expression levels of genes encoding K+ ion channels will help to better understand the pathological mechanisms that occur during epilepsy. In the SE experimental model created, it is believed that an increase in mRNA expression of KCNQ1 and KCNQ3 will lead to drug therapy studies planned for the future.
Anahtar Kelimeler
Kaynakça
- Brading AF. Spontaneous activity of lower urinary tract smooth muscles: correlation between ion channels and tissue function. The Journal of physiology.2006;570:13-22.
- Lerche H, Jurkat‐Rott K, Lehmann‐Horn F. Ion channels and epilepsy. American journal of medical genetics.2001;106:146-59.
- Iannetti P, Farello G, Verrotti A. Editorial–Channelopathies: a link between brain and heart: the model of epilepsy. Eur Rev Med Pharmacol Sci.2017;21:5523-26.
- Vizuete AFK, Hennemann MM, Gonçalves CA, De Oliveira DL. Phase-dependent astroglial alterations in Li–pilocarpine-induced status epilepticus in young rats. Neurochemical research. 2017;42:2730-42.
- Hitiris N, Mohanraj R, Norrie J, Sills GJ, Brodie MJ. Predictors of pharmacoresistant epilepsy. Epilepsy research.2007;75:192-196. .Hartmann M, Decking UKM. Blocking Na+–H+ exchange by cariporide reduces Na+-overload in ischemia and is cardioprotective. Journal of molecular and cellular cardiology.1999;31:1985-95.
- Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Keating MT. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell.1995;80:805-11.
- D'Adamo MC, Catacuzzeno L, Di Giovanni G, Franciolini F, Pessia M. K+ channelepsy: progress in the neurobiology of potassium channels and epilepsy. Frontiers in cellular neuroscience.2013;7:134.
- Jespersen T, Grunnet M, Olesen SP. The KCNQ1 potassium channel: from gene to physiological function. Physiology.2005;20:408-16.
- Berkovic SF, Mulley JC, Scheffer IE, Petrou S. Human epilepsies: interaction of genetic and acquired factors. Trends in neurosciences.2006;29:391-97.
- Rogawski MA. KCNQ2/KCNQ3 K+ channels and the molecular pathogenesis of epilepsy: implications for therapy. Trends in neurosciences.2000;23:393-98.
- Nashef L, Hindocha N, MakoffA. Risk factors in sudden death in epilepsy (SUDEP): the quest for mechanisms. Epilepsia.2007;48:859-71.
- Kim JE, Yeo SI, Ryu HJ, Kim MJ, Kim DS, Jo SM, Kang TC. Astroglial loss and edema formation in the rat piriform cortex and hippocampus following pilocarpine‐induced status epilepticus. Journal of Comparative Neurology. 2010;518:4612-28.
- Liu J, Wang A, Li L, Huang Y, Xue P, Hao A. Oxidative stress mediates hippocampal neuron death in rats after lithium–pilocarpine-induced status epilepticus. Seizure.2010;19:165-72.
- Curia G, Longo D, Biagini G, Jones RS, Avoli M. The pilocarpine model of temporal lobe epilepsy. J Neurosci Methods.2008;172:143-57.
- Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol. 1972;32:281-94.
- Glien M, Brandt C, Potschka H, Voigt H, Ebert U, Löscher W. Repeated low-dose treatment of rats with pilocarpin: low mortality but high proportion of rats developing epilepsy. Epilepsy Res. 2001;46:111-9.
- Suchomelova L, Baldwin RA, Kubova H, Thompson KW, Sankar R, Wasterlain CG. Treatment of experimental status epilepticus in immature rats. Pediatr Res. 2006;59:237-43.
- Akay A, Sümer-Turanlıgil NC, Uyanıkgil Y.İyon Kanalları ve Epilepsi Patojenezindeki Rolleri. Arşiv Kaynak Tarama Dergisi.2010;19:72-84.
- Brenner R, Wilcox KS. Potassium channelopathies of epilepsy. In Jasper's Basic Mechanisms of the Epilepsies. 4th edition. 2012 ; National Center for Biotechnology Information (US).
- Blume WT, Lüders HO, Mizrahi E, Tassinari, van Emde Boas W, Engel Jr, Ex‐officio J. Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology. Epilepsia.2001;42:1212-18.
- Shah MM, Anderson AE, Leung V, Lin X, Johnston D. Seizure-induced plasticity of h channels in entorhinal cortical layer III pyramidal neurons. Neuron.2004;44:495-508.
- Sonat FA, Balcı F. Sıçanlarda Pilocarpin ile Oluşturulan Epilepside Topiramatın Nöronlar Üzerine Etkisi. Uludağ Üniversitesi Veteriner Fakültesi Dergisi.2010;29:1-7.
- Jentsch TJ. Neuronal KCNQ potassium channels: physislogy and role in disease. Nature Reviews Neuroscience.2000;1:21-30.
- Seebohm G, Scherer CR, Busch A, Lerche C. Identification of Specific Pore Residues Mediating KCNQ1 Inactivation A Novel Mechanismforlong QT syndrome. Journal of Biological Chemistry.2001;276:13600-605.
- Chouabe C, Neyroud N, Richard P, Denjoy I, Hainque B, Romey G, Barhanin J. Novel mutations in KvLQT1 that affect I Ks activation through interactions with Isk. Cardiovascular research.2000;45:971-80.
- Wang Q, Curran M, Splawski I, Burn TC, Millholland JM, VanRaay TJ, Schwartz PJ. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nature genetics.1996;12:17-23.
- Delmas P, Brown DA. Pathways modulating neural KCNQ/M (Kv7) potassium channels. Nature Reviews Neuroscience.2005;6:850-62.
- Luo X, Xiao J, Lin H, Lu Y, Yang B, Wang Z. Genomic structure, transcriptional control, and tissue distribution of HERG1 and KCNQ1 genes. American Journal of Physiology-Heart and Circulatory Physiology.2008;294(3): H1371-H1380.
- Goldman AM, Glasscock E, Yoo J, Chen TT, Klassen TL, Noebels JL. Arrhythmia in heart and brain: KCNQ1 mutations link epilepsy and sudden unexplained death. Science translational medicine.2009;1:2ra6-2ra6.
- Hong K, Piper DR, Diaz-Valdecantos A, Brugada J, Oliva A, Burashnikov E, Sachse F. De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero. Cardiovascular Research.2005;68:433-40.
- Chang Q, Wang J, Li Q, Kim Y, Zhou B, Wang Y, Lin X. Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange‐Nielsen deafness syndrome. EMBO molecular medicine. 2015;7:1077-86.
- Tiron C, Campuzano O, Pérez-Serra A, Mademont I, Coll M, Allegue C, Brugada R. Further evidence of the association between LQT syndrome and epilepsy in a family with KCNQ1 pathogenic variant.Seizure.2015;25:65-7.
- Schroeder BC, Kubisch C, Stein V, Jentsch TJ. Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature. 1998;396:687-90.
- Su T, Cong WD, Long YS, Luo AH, Sun WW, Deng WY, Liao WP. Altered expression of voltage-gated potassium channel 4.2 and voltage-gated potassium channel 4-interacting protein, and changes in intracellular calcium levels following lithium-pilocarpine-induced status epilepticus.Neuroscience.2008;157:566-76.
- Saganich MJ, Machado E, Rudy B. Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain. Journal of Neuroscience.2001;21:4609-24.
- Tinel N, Lauritzen I, Chouabe, Lazdunski M, Borsotto M. The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3. FEBS letters. 1998;438:171-76.
- Yang WP, Levesque PC, Little WA, Conder ML, Ramakrishnan P, Neubauer MG, Blanar MA. Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy. Journal of Biological Chemistry.1998;273:19419-423.
- Yavuz ENV, Baykan B. Epilepsi, Moleküler Mekanizmalar ve İlgili Nöromediatörler. Türkiye Klinikleri Neurology-Special Topics.2010;3:38-42.
- Walker MC, Schorge S, Kullmann DM, Wykes RC, Heeroma JH, Mantoan L. Gene therapy in status epilepticus. Epilepsia.2013;54:43-45.
- Villa C, Combi R. Potassium channels and human epileptic phenotypes: an updated overview. Frontiers in cellular neuroscience.2016;10:81.
- Kudin AP, Debska‐Vielhaber G, Vielhaber S, Elger CE, Kunz WS. The mechanism of neuroprotection by topiramate in an animal model of epilepsy. Epilepsia.2004;45:1478-87.
Yıl 2020,
Cilt: 45 Sayı: 4, 1580 - 1586, 27.12.2020
Öz
Amaç: Status epileptikus (SE) 30 dakikadan daha uzun süre tekrarlayan jeneralize konvulziyonlarla birlikte çocuklarda oldukça yaygın bir şekilde görülen nörolojik bir hastalıktır ve kontrol edilmediğinde, beyinde nöronal hasarlar meydana gelir. Bu çalışmanın amacı SE sonrası akut dönemde KCNQ1 ve KCNQ3 gen ekspresyon seviyelerindeki değişiklikleri değerlendirmektir.
Gereç ve Yöntem: Sıçanlarda Li-Pc ile deneysel SE modeli oluşturuldu. Çalışmada; SE, kontrol ve sham grupları olmak üzere 3 grupta dişi Wistar albino [250–350 gr, 21 adet (n=7)] sıçan kullanıldı. Beyin dokularından elde edilen total RNA, cDNA'ya çevrilerek KCNQ1 ve KCNQ3 genlerinin kantitatif gerçek zamanlı PCR (qRT-PCR) yöntemi ile gen ekspresyon değişimleri değerlendirildi.
Bulgular: İstatistiksel olarak SE grubunda; kontrol ve sham grubuna kıyasla KCNQ1 ve KCNQ3 genlerinin ekspresyon seviyelerinde anlamlı oranda farklılık görüldü. Deney grubunun KCNQ1 ve KCNQ3 gen ekspresyon düzeyleri diğer gruplardan yüksek bulundu.
Sonuç: K+ iyon kanallarını kodlayan genlerin mRNA ekspresyon seviyelerindeki değişikliklerin belirlenmesi epilepsi sırasında oluşan patolojik mekanizmaların daha iyi anlaşılmasına yardımcı olacaktır. Oluşturulan SE deneysel modelde KCNQ1 ve KCNQ3 mRNA ekpresyonlarında artış saptanması ileride yapılması planlanan tedaviye yönelik ilaç çalışmalarına yol göstereceğine inanılmaktadır.
Anahtar Kelimeler
Kaynakça
- Brading AF. Spontaneous activity of lower urinary tract smooth muscles: correlation between ion channels and tissue function. The Journal of physiology.2006;570:13-22.
- Lerche H, Jurkat‐Rott K, Lehmann‐Horn F. Ion channels and epilepsy. American journal of medical genetics.2001;106:146-59.
- Iannetti P, Farello G, Verrotti A. Editorial–Channelopathies: a link between brain and heart: the model of epilepsy. Eur Rev Med Pharmacol Sci.2017;21:5523-26.
- Vizuete AFK, Hennemann MM, Gonçalves CA, De Oliveira DL. Phase-dependent astroglial alterations in Li–pilocarpine-induced status epilepticus in young rats. Neurochemical research. 2017;42:2730-42.
- Hitiris N, Mohanraj R, Norrie J, Sills GJ, Brodie MJ. Predictors of pharmacoresistant epilepsy. Epilepsy research.2007;75:192-196. .Hartmann M, Decking UKM. Blocking Na+–H+ exchange by cariporide reduces Na+-overload in ischemia and is cardioprotective. Journal of molecular and cellular cardiology.1999;31:1985-95.
- Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Keating MT. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell.1995;80:805-11.
- D'Adamo MC, Catacuzzeno L, Di Giovanni G, Franciolini F, Pessia M. K+ channelepsy: progress in the neurobiology of potassium channels and epilepsy. Frontiers in cellular neuroscience.2013;7:134.
- Jespersen T, Grunnet M, Olesen SP. The KCNQ1 potassium channel: from gene to physiological function. Physiology.2005;20:408-16.
- Berkovic SF, Mulley JC, Scheffer IE, Petrou S. Human epilepsies: interaction of genetic and acquired factors. Trends in neurosciences.2006;29:391-97.
- Rogawski MA. KCNQ2/KCNQ3 K+ channels and the molecular pathogenesis of epilepsy: implications for therapy. Trends in neurosciences.2000;23:393-98.
- Nashef L, Hindocha N, MakoffA. Risk factors in sudden death in epilepsy (SUDEP): the quest for mechanisms. Epilepsia.2007;48:859-71.
- Kim JE, Yeo SI, Ryu HJ, Kim MJ, Kim DS, Jo SM, Kang TC. Astroglial loss and edema formation in the rat piriform cortex and hippocampus following pilocarpine‐induced status epilepticus. Journal of Comparative Neurology. 2010;518:4612-28.
- Liu J, Wang A, Li L, Huang Y, Xue P, Hao A. Oxidative stress mediates hippocampal neuron death in rats after lithium–pilocarpine-induced status epilepticus. Seizure.2010;19:165-72.
- Curia G, Longo D, Biagini G, Jones RS, Avoli M. The pilocarpine model of temporal lobe epilepsy. J Neurosci Methods.2008;172:143-57.
- Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol. 1972;32:281-94.
- Glien M, Brandt C, Potschka H, Voigt H, Ebert U, Löscher W. Repeated low-dose treatment of rats with pilocarpin: low mortality but high proportion of rats developing epilepsy. Epilepsy Res. 2001;46:111-9.
- Suchomelova L, Baldwin RA, Kubova H, Thompson KW, Sankar R, Wasterlain CG. Treatment of experimental status epilepticus in immature rats. Pediatr Res. 2006;59:237-43.
- Akay A, Sümer-Turanlıgil NC, Uyanıkgil Y.İyon Kanalları ve Epilepsi Patojenezindeki Rolleri. Arşiv Kaynak Tarama Dergisi.2010;19:72-84.
- Brenner R, Wilcox KS. Potassium channelopathies of epilepsy. In Jasper's Basic Mechanisms of the Epilepsies. 4th edition. 2012 ; National Center for Biotechnology Information (US).
- Blume WT, Lüders HO, Mizrahi E, Tassinari, van Emde Boas W, Engel Jr, Ex‐officio J. Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology. Epilepsia.2001;42:1212-18.
- Shah MM, Anderson AE, Leung V, Lin X, Johnston D. Seizure-induced plasticity of h channels in entorhinal cortical layer III pyramidal neurons. Neuron.2004;44:495-508.
- Sonat FA, Balcı F. Sıçanlarda Pilocarpin ile Oluşturulan Epilepside Topiramatın Nöronlar Üzerine Etkisi. Uludağ Üniversitesi Veteriner Fakültesi Dergisi.2010;29:1-7.
- Jentsch TJ. Neuronal KCNQ potassium channels: physislogy and role in disease. Nature Reviews Neuroscience.2000;1:21-30.
- Seebohm G, Scherer CR, Busch A, Lerche C. Identification of Specific Pore Residues Mediating KCNQ1 Inactivation A Novel Mechanismforlong QT syndrome. Journal of Biological Chemistry.2001;276:13600-605.
- Chouabe C, Neyroud N, Richard P, Denjoy I, Hainque B, Romey G, Barhanin J. Novel mutations in KvLQT1 that affect I Ks activation through interactions with Isk. Cardiovascular research.2000;45:971-80.
- Wang Q, Curran M, Splawski I, Burn TC, Millholland JM, VanRaay TJ, Schwartz PJ. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nature genetics.1996;12:17-23.
- Delmas P, Brown DA. Pathways modulating neural KCNQ/M (Kv7) potassium channels. Nature Reviews Neuroscience.2005;6:850-62.
- Luo X, Xiao J, Lin H, Lu Y, Yang B, Wang Z. Genomic structure, transcriptional control, and tissue distribution of HERG1 and KCNQ1 genes. American Journal of Physiology-Heart and Circulatory Physiology.2008;294(3): H1371-H1380.
- Goldman AM, Glasscock E, Yoo J, Chen TT, Klassen TL, Noebels JL. Arrhythmia in heart and brain: KCNQ1 mutations link epilepsy and sudden unexplained death. Science translational medicine.2009;1:2ra6-2ra6.
- Hong K, Piper DR, Diaz-Valdecantos A, Brugada J, Oliva A, Burashnikov E, Sachse F. De novo KCNQ1 mutation responsible for atrial fibrillation and short QT syndrome in utero. Cardiovascular Research.2005;68:433-40.
- Chang Q, Wang J, Li Q, Kim Y, Zhou B, Wang Y, Lin X. Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange‐Nielsen deafness syndrome. EMBO molecular medicine. 2015;7:1077-86.
- Tiron C, Campuzano O, Pérez-Serra A, Mademont I, Coll M, Allegue C, Brugada R. Further evidence of the association between LQT syndrome and epilepsy in a family with KCNQ1 pathogenic variant.Seizure.2015;25:65-7.
- Schroeder BC, Kubisch C, Stein V, Jentsch TJ. Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature. 1998;396:687-90.
- Su T, Cong WD, Long YS, Luo AH, Sun WW, Deng WY, Liao WP. Altered expression of voltage-gated potassium channel 4.2 and voltage-gated potassium channel 4-interacting protein, and changes in intracellular calcium levels following lithium-pilocarpine-induced status epilepticus.Neuroscience.2008;157:566-76.
- Saganich MJ, Machado E, Rudy B. Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain. Journal of Neuroscience.2001;21:4609-24.
- Tinel N, Lauritzen I, Chouabe, Lazdunski M, Borsotto M. The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3. FEBS letters. 1998;438:171-76.
- Yang WP, Levesque PC, Little WA, Conder ML, Ramakrishnan P, Neubauer MG, Blanar MA. Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy. Journal of Biological Chemistry.1998;273:19419-423.
- Yavuz ENV, Baykan B. Epilepsi, Moleküler Mekanizmalar ve İlgili Nöromediatörler. Türkiye Klinikleri Neurology-Special Topics.2010;3:38-42.
- Walker MC, Schorge S, Kullmann DM, Wykes RC, Heeroma JH, Mantoan L. Gene therapy in status epilepticus. Epilepsia.2013;54:43-45.
- Villa C, Combi R. Potassium channels and human epileptic phenotypes: an updated overview. Frontiers in cellular neuroscience.2016;10:81.
- Kudin AP, Debska‐Vielhaber G, Vielhaber S, Elger CE, Kunz WS. The mechanism of neuroprotection by topiramate in an animal model of epilepsy. Epilepsia.2004;45:1478-87.
Toplam 41 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Araştırma |
| Yazarlar | |
| Yayımlanma Tarihi | 27 Aralık 2020 |
| Kabul Tarihi | 16 Ağustos 2020 |
| Yayımlandığı Sayı | Yıl 2020 Cilt: 45 Sayı: 4 |
