THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY

utkan, tijen; Karson, Ayse; ARICIOĞLU, FEYZA; ATES, NURBAY; Akman, Özlem

doi:10.26650/IUITFD.904146

THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY

Özlem AKMAN, (Demiroğlu Bilim Üniversitesi, Tıp Fakültesi, Fizyoloji Anabilim Dalı, İstanbul, Türkiye)

Tijen UTKAN, (Kocaeli Üniversitesi, Tıp Fakültesi, Farmakoloji Anabilim Dalı, Kocaeli, Türkiye)

Feyza ARICIOĞLU, (Marmara Üniversitesi Eczacılık Fakültesi, Farmakoloji Anabilim Dalı, İstanbul, Türkiye)

Nurbay ATEŞ, (Kocaeli Üniversitesi, Tıp Fakültesi, Fizyoloji Anabilim Dalı, Kocaeli, Türkiye)

Ayşe KARSON (Kocaeli Üniversitesi, Tıp Fakültesi, Fizyoloji Anabilim Dalı, Kocaeli, Türkiye)

İstanbul Tıp Fakültesi Dergisi

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Yıl: 2022 Cilt: 85 Sayı: 1 Sayfa Aralığı: 15 - 21 Metin Dili: İngilizce DOI: 10.26650/IUITFD.904146 İndeks Tarihi: 27-08-2022

THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY

Öz:

Objective: Studies on the actions of exogenous agmatine in experimental models have shown its anti-convulsant effects. However, there are no findings regarding the influence of agmatine on absence epilepsy. Therefore, we investigated the effects of the agmatine in the occurrence of spike-and-wave discharges (SWDs) in the Wistar Albino Glaxo Rijswijk rats (WAG/Rij) model of genetic absence epilepsy. Materials and Methods: Three different doses (20, 40 or 80 mg/kg) of agmatine or saline were administered intraperitoneally to the adult WAG/Rij rats, and electroencephalography (EEG) was recorded for 2.5 hours. The number and the mean and cumulative durations of SWDs were measured. The SWD frequency characteristics were quantified by means of average power-spectra of the first 2nd segments of the SWD complexes before and after the effective dose of agmatine. Results: Agmatine, administered 80 mg/kg systemically, temporarily increased the number and cumulative duration of SWDs compared with saline injected WAG/Rij rats. This effect of agmatine, however, was not associated with any change in the frequency characteristics of the SWD complexes. There was no effect on neither the incidence nor the cumulative duration of SWDs when agmatine administered in lower doses (20 or 40 mg/kg). Conclusion: Higher doses of agmatine temporarily and slightly increase the incidence of SWDs in WAG/Rij rats, which may suggest its possible aggravating activity in absence epilepsy patients through its activity on adrenergic, serotonergic and AMPA receptors.

Anahtar Kelime:

AGMATİNİN GENETİK BİR ABSANS EPİLEPSİ MODELİNDE DİKEN-VE-DALGA DEŞARJLAR ÜZERİNE ETKİSİ

Öz:

Amaç: Deneysel modellerde yapılan araştırmalar ekzojen agmatinin anti-konvülzan etkilerinin olduğunu göstermiştir. Ancak, agmatinin absans epilepsisi üzerindeki etkisine dair herhangi bir veri bulunmamaktadır. Bu çalışmada, agmatinin absans epilepsinin genetik bir modeli olan Wistar Albino Glaxo Rijswijk (WAG/ Rij) ırkı sıçanlarda Diken-ve-Dalga Deşarjlar (DDD) üzerine olan etkilerini araştırdık. Gereç ve Yöntem: Yetişkin WAG/Rij sıçanlarda periton içine 3 farklı doz agmatin (20, 40 ya da 80 mg/kg) ya da serum fizyolojik uygulandı ve 2,5 saat boyunca elektroensefalografi (EEG) kaydedildi. Elde edilen EEG kayıtlarında DDD’lerin sayısı, ortalama ve kümülatif süreleri değerlendirildi. DDD’lerin frekans özellikleri, etkili agmatin dozundan önce ve sonra, DDD aktivitesinin ilk iki saniyelik bölümlerinin ortalama güç spektrumları hesaplanarak karşılaştırıldı. Bulgular: WAG/Rij sıçanlara sistemik olarak uygulanan 80 mg/kg agmatin DDD’lerin sayısını ve kümülatif süresini serum fizyolojik uygulanan gruba göre geçici olarak arttırdı. Ancak, agmatinin bu etkisi DDD’lerin frekans özelliklerindeki bir değişiklikle ilişki bulunmadı. Daha düşük dozlarda uygulanan agmatin (20 veya 40 mg/kg) ise DDD’lerin sayı ve süresine değişikliğe yol açmadı. Sonuç: Yüksek doz agmatin WAG/Rij ırkı sıçanlarda DDD insidansını geçiçi olarak arttırmaktadır. Bu sonuçlar, agmatinin absans epilepsisi hastalarında adrenerjik, serotonerjik ve AMPA reseptörleri aracılığı ile olası bir kötüleştirici etki gösterebileceğini işaret etmektedir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. van Luijtelaar G, Onat FY, Gallagher MJ. Animal models of absence epilepsies: what do they model and do sex and sex hormones matter? Neurobiol Dis 2014;72PtB:167-79. [CrossRef]
2. van Luijtelaar G, Zobeiri M. Progress and outlooks in a genetic absence epilepsy model (WAG/Rij). Curr Med Chem 2014;21(6):704-21. [CrossRef]
3. Smyk MK, van Luijtelaar G. Circadian Rhythms and Epilepsy: A Suitable Case for Absence Epilepsy. Front Neurol 2020;11 245. 2020/04/28. [CrossRef]
4. Russo E, Citraro R, Constanti A, Leo A, Lüttjohann A, van Luijtelaar G, et al. Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development. Neurosci Biobehav Rev 2016;71:388-408. [CrossRef]
5. Moeller F, Stephani U, Siniatchkin M. Simultaneous EEG and fMRI recordings (EEG-fMRI) in children with epilepsy. Epilepsia 2013;54(6):971-82. [CrossRef]
6. Meeren HK, Pijn JP, Van Luijtelaar EL, Coenen AM, Lopes da Silva FH. Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. J Neurosci 2002;22(4):1480-95. [CrossRef]
7. Polack PO, Guillemain I, Hu E, Deransart C, Depaulis A, Charpier S. Deep layer somatosensory cortical neurons initiate spike-and-wave discharges in a genetic model of absence seizures. J Neurosci 2007;27(24):6590-9. [CrossRef]
8. Cope DW, Di Giovanni G, Fyson SJ, Orbán G, Errington AC, Lorincz ML, et al. Enhanced tonic GABAA inhibition in typical absence epilepsy. Nat Med 2009;15(12):1392-8. [CrossRef]
9. Citraro R, Russo E, Gratteri S, Di Paola ED, Ibbadu GF, Curinga C, et al. Effects of non-competitive AMPA receptor antagonists injected into some brain areas of WAG/Rij rats, an animal model of generalized absence epilepsy. Neuropharmacology 2006;51(6):1058-67. [CrossRef]
10. Peeters BW, van Rijn CM, Vossen JM, Coenen AM. Involvement of NMDA receptors in non-convulsive epilepsy in WAG/Rij rats. Life Sci 1990;47(6):523-9. [CrossRef]
11. Yavuz M, Aydın B, Çarçak N, Akman Ö, Raci Yananlı H, Onat F. Atipamezole, a specific α. Epilepsia 2020;61(12):2825-35. [CrossRef]
12. Jakus R, Graf M, Juhasz G, Gerber K, Levay G, Halasz P, et al. 5-HT2C receptors inhibit and 5-HT1A receptors activate the generation of spike-wave discharges in a genetic rat model of absence epilepsy. Exp Neurol 2003;184(2):964-72. [CrossRef]
13. Sitnikova E, van Luijtelaar G. Reduction of adrenergic neurotransmission with clonidine aggravates spike-wave seizures and alters activity in the cortex and the thalamus in WAG/Rij rats. Brain Res Bull 2005;64(6):533-40. [CrossRef]
14. Neis VB, Rosa PB, Olescowicz G, Rodrigues ALS. Therapeutic potential of agmatine for CNS disorders. Neurochem Int 2017;108:318-31. [CrossRef]
15. Piletz JE, Aricioglu F, Cheng JT, Fairbanks CA, Gilad VH, Haenisch B, et al. Agmatine: clinical applications after 100 years in translation. Drug Discov Today 2013;18(17-18): 880- 93. [CrossRef]
16. Uzbay TI. The pharmacological importance of agmatine in the brain. Neurosci Biobehav Rev 2012;36(1):502-19. [CrossRef] 17. Galgano F, Caruso M, Condelli N, Favati F. Focused review:
agmatine in fermented foods. Front Microbiol 2012;3:199. [CrossRef]
18. Weng XC, Gai XD, Zheng JQ, Li J. Agmatine blocked voltage-gated calcium channel in cultured rat hippocampal neurons. Acta Pharmacol Sin 2003;24(8):746-50.
19. Galea E, Regunathan S, Eliopoulos V, Feinstein DL, Reis DJ. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. Biochem J 1996;316(Pt 1):247-9. [CrossRef]
20. Barua S, Kim JY, Kim JH, Lee JE. Therapeutic Effect of Agmatine on Neurological Disease: Focus on Ion Channels and Receptors. Neurochem Res 2019;44(4):735-50. [CrossRef]
21. Aricioglu F, Kan B, Yillar O, Korcegez E, Berkman K. Effect of agmatine on electrically and chemically induced seizures in mice. Ann N Y Acad Sci 2003;1009:141-6. [CrossRef]
22. Demehri S, Homayoun H, Honar H, Riazi K, Vafaie K, Roushanzamir F, et al. Agmatine exerts anticonvulsant effect in mice: modulation by alpha 2-adrenoceptors and nitric oxide. Neuropharmacology 2003;45(4):534-42. [CrossRef]
23. Aricioglu F, Altunbas H. Is agmatine an endogenous anxiolytic/antidepressant agent? Ann N Y Acad Sci 2003;1009:136-40. [CrossRef]
24. Akman O, Gulcebi MI, Carcak N, Ketenci Ozatman S, Eryigit T, Moshé SL, et al. The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy. Epilepsia 2015;56(11):1793-802. [CrossRef]
25. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 6th ed ed.: Elsevier, 2007.
26. Akman O, Karson A, Aker RG, Ates N, Onat FY. Perirhinal cortical kindling in rats with genetic absence epilepsy. Neuroscience Letters 2010;479(1):74-8. [CrossRef]
27. Akman O, Demiralp T, Ates N, Onat FY. Electroencephalographic differences between WAG/ Rij and GAERS rat models of absence epilepsy. Epilepsy Research 2010;89(2-3):185-93. [CrossRef]
28. Rigoulot MA, Boehrer A, Nehlig A. Effects of topiramate in two models of genetically determined generalized epilepsy, the GAERS and the Audiogenic Wistar AS. Epilepsia 2003;44(1):14-9. [CrossRef]
29. Smyk MK, Coenen AM, Lewandowski MH, van Luijtelaar G. Endogenous rhythm of absence epilepsy: relationship with general motor activity and sleep-wake states. Epilepsy Res 2011;93(2-3):120-7. [CrossRef]
30. Peeters BW, Ramakers GM, Vossen JM, Coenen AM. The WAG/Rij rat model for nonconvulsive absence epilepsy: involvement of nonNMDA receptors. Brain Res Bull 1994;33(6):709-13. [CrossRef]
31. Russo E, Citraro R, De Fazio S, Marra R, Gitto R, Chimirri A, et al. Enhancement of anti-absence effects of ethosuximide by low doses of a noncompetitive alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist in a genetic animal model of absence epilepsy. Epilepsy Behav 2008;13(2):295-9. [CrossRef]
32. Kennard JT, Barmanray R, Sampurno S, Ozturk E, Reid CA, Paradiso L, et al. Stargazin and AMPA receptor membrane expression is increased in the somatosensory cortex of Genetic Absence Epilepsy Rats from Strasbourg. Neurobiol Dis 2011;42(1):48-54. [CrossRef]
33. Neis VB, Moretti M, Bettio LE, Ribeiro CM, Rosa PB, Gonçalves FM, et al. Agmatine produces antidepressantlike effects by activating AMPA receptors and mTOR signaling. Eur Neuropsychopharmacol 2016;26(6):959-71. [CrossRef]
34. Dias Elpo Zomkowski A, Oscar Rosa A, Lin J, Santos AR, Calixto JB, Lúcia Severo Rodrigues A. Evidence for serotonin receptor subtypes involvement in agmatine antidepressant like-effect in the mouse forced swimming test. Brain Res 2004;1023(2):253-63. [CrossRef]
35. Filakovszky J, Gerber K, Bagdy G. A serotonin-1A receptor agonist and an N-methyl-D-aspartate receptor antagonist oppose each others effects in a genetic rat epilepsy model. Neurosci Lett 1999;261(1-2):89-92. [CrossRef]
36. Ramakers GM, Peeters BW, Vossen JM, Coenen AM. CNQX, a new non-NMDA receptor antagonist, reduces spike wave discharges in the WAG/Rij rat model of absence epilepsy. Epilepsy Res 1991;9(2):127-31. [CrossRef]
37. Gunes H, Ozdemir E, Arslan G. Coenzyme Q10 increases absence seizures in WAG/Rij rats: The role of the nitric oxide pathway. Epilepsy Res 2019;154:69-73. [CrossRef]
38. Przewlocka B, Lason W, van Luijtelaar G, Coenen T, Przewlocki R. The role of nitric oxide in genetic model of absence epilepsy in rats. Neuroscience Research Communications Article 1996;18(2):125-31. [CrossRef]

APA	Akman Ö, utkan t, ARICIOĞLU F, ATES N, Karson A (2022). THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY. , 15 - 21. 10.26650/IUITFD.904146
Chicago	Akman Özlem,utkan tijen,ARICIOĞLU FEYZA,ATES NURBAY,Karson Ayse THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY. (2022): 15 - 21. 10.26650/IUITFD.904146
MLA	Akman Özlem,utkan tijen,ARICIOĞLU FEYZA,ATES NURBAY,Karson Ayse THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY. , 2022, ss.15 - 21. 10.26650/IUITFD.904146
AMA	Akman Ö,utkan t,ARICIOĞLU F,ATES N,Karson A THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY. . 2022; 15 - 21. 10.26650/IUITFD.904146
Vancouver	Akman Ö,utkan t,ARICIOĞLU F,ATES N,Karson A THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY. . 2022; 15 - 21. 10.26650/IUITFD.904146
IEEE	Akman Ö,utkan t,ARICIOĞLU F,ATES N,Karson A "THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY." , ss.15 - 21, 2022. 10.26650/IUITFD.904146
ISNAD	Akman, Özlem vd. "THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY". (2022), 15-21. https://doi.org/10.26650/IUITFD.904146

APA	Akman Ö, utkan t, ARICIOĞLU F, ATES N, Karson A (2022). THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY. İstanbul Tıp Fakültesi Dergisi, 85(1), 15 - 21. 10.26650/IUITFD.904146
Chicago	Akman Özlem,utkan tijen,ARICIOĞLU FEYZA,ATES NURBAY,Karson Ayse THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY. İstanbul Tıp Fakültesi Dergisi 85, no.1 (2022): 15 - 21. 10.26650/IUITFD.904146
MLA	Akman Özlem,utkan tijen,ARICIOĞLU FEYZA,ATES NURBAY,Karson Ayse THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY. İstanbul Tıp Fakültesi Dergisi, vol.85, no.1, 2022, ss.15 - 21. 10.26650/IUITFD.904146
AMA	Akman Ö,utkan t,ARICIOĞLU F,ATES N,Karson A THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY. İstanbul Tıp Fakültesi Dergisi. 2022; 85(1): 15 - 21. 10.26650/IUITFD.904146
Vancouver	Akman Ö,utkan t,ARICIOĞLU F,ATES N,Karson A THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY. İstanbul Tıp Fakültesi Dergisi. 2022; 85(1): 15 - 21. 10.26650/IUITFD.904146
IEEE	Akman Ö,utkan t,ARICIOĞLU F,ATES N,Karson A "THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY." İstanbul Tıp Fakültesi Dergisi, 85, ss.15 - 21, 2022. 10.26650/IUITFD.904146
ISNAD	Akman, Özlem vd. "THE EFFECT OF AGMATINE ON SPIKE-AND-WAVE DISCHARGES IN A GENETIC MODEL OF ABSENCE EPILEPSY". İstanbul Tıp Fakültesi Dergisi 85/1 (2022), 15-21. https://doi.org/10.26650/IUITFD.904146