The Role of Rho/Rho-Kinase Pathway in the Pathophysiology of Absence Epilepsy

Conclusion: The findings indicate that the Rho-kinase pathway may play a role in the generation of absence seizures, and that the suppressive effect of Y-27632 on SWDs may be a potential therapeutic target for this anti-absent effect.

📌 3 Key Takeaways

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Objective & Hypothesis:bjectives: Rho/Rho-kinase (ROCK) signaling has been shown to contribute to neuroinflammation, epileptogenesis, and seizures in convulsivetype epilepsy models.

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Key Findings & Data:The aim of this study was to investigate ROCK activity in brain regions involved in spike-and-wave discharge (SWD) generation and the effects of the Rho-kinase inhibitor, Y-27632, on ROCK activity in genetic absence epilepsy rats from Strasburg (GAERS).

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Conclusion & Impact:Conclusion: The findings indicate that the Rho-kinase pathway may play a role in the generation of absence seizures, and that the suppressive effect of Y-27632 on SWDs may be a potential therapeutic target for this anti-absent effect.

🔬Design:Modeling & Simulation

📍Scope:Comprehensive Sample

⚙️Variables:Domain Parameters

Abstract

bjectives: Rho/Rho-kinase (ROCK) signaling has been shown to contribute to neuroinflammation, epileptogenesis, and seizures in convulsivetype epilepsy models. However, this pathway has not been investigated in the pathophysiology of absence epilepsy. The aim of this study was to investigate ROCK activity in brain regions involved in spike-and-wave discharge (SWD) generation and the effects of the Rho-kinase inhibitor, Y-27632, on ROCK activity in genetic absence epilepsy rats from Strasburg (GAERS). Methods: ROCK activity in the somatosensorial cortex, hippocampus, and thalamus was measured using an enzyme-linked immunosorbent assay (ELISA). An intracerebroventricular (i.c.v.) injection of Y-27632 was administered at a dose of 20 nmol/5 μl and changes in ROCK activity were assessed. To evaluate the effect of Y-27632 on SWDs, i.c.v. 20 nmol and 60 nmol doses of Y-27632 were administered to the GAERS subjects and electroencephalography was performed. Results: ROCK activity was elevated in the somatosensory cortex in the GAERS study subjects, and the Rho-kinase enzyme inhibitor, Y-27632, suppressed this increase. In addition, Y-27632 significantly reduced the total and mean duration of SWDs compared with the control group. Conclusion: The findings indicate that the Rho-kinase pathway may play a role in the generation of absence seizures, and that the suppressive effect of Y-27632 on SWDs may be a potential therapeutic target for this anti-absent effect.

Özet

Amaç: Rho/Rho-kinaz (ROCK) hücre içi sinyal yolağının nöroinflamasyon, epileptogenez ve konvülzif tip epilepsilerde nöbetlerle ilişkili olduğu deneysel hayvan modellerinde gösterilmiştir. Ancak bu yolağın absans epilepsisinin patofizyolojisindeki rolü henüz aydınlatılmamıştır. Burada, Strazburg kökenli genetik absans epilepsili sıçanlarda (GAERS) diken-ve-yavaş-dalga deşarjların (DDD) ortaya çıkışından sorumlu beyin bölgelerindeki, ROCK aktivitesinin değerlendirilmesi ve Rho-kinaz enzim inhibitörü Y-27632’in ROCK aktivitesi üzerindeki etkisinin araştırılması amaçlanmıştır. Gereç ve Yöntem: ROCK aktivitesi, GAERS sıçanlarda somatosensoriyel korteks, hipokampüs ve talamusta ELISA (Enzyme-linked immunosorbent assay) yöntemiyle ölçülmüştür. Bununla birlikte bir grup GAERS sıçana intraserebroventriküler (i.s.v.) olarak 20 nmol/5μl dozunda Y-27632 uygulanmış ve ROCK enzim aktivitesindeki değişiklik değerlendirilmiştir. Ek olarak, i.s.v. yoldan verilen Y-27632’nin DDD’ler üzerindeki etkisinin değerlendirilmesi amacıyla GAERS sıçanlara iki farklı dozda (20 nmol ve 60 nmol) Y-27632 uygulanmış ve EEG kaydı alınmıştır. Bulgular: GAERS sıçanların somatosensoriyel korteksinde ROCK aktivitesi artmıştır ve Rho-kinaz enzim inhibitörü Y-27632 bu artışı baskılamıştır. Buna ek olarak, i.s.v. olarak uygulanan Y-2732 DDD’lerin toplam ve ortalama süresini kontrol grubuna göre anlamlı derecede azaltmıştır. Sonuç: Bulgularımız, Rho-kinaz sinyal yolağının absans nöbetlerin ortaya çıkışında rol alabileceğini ve dahası Y-27632’nin DDD’leri baskılayıcı etkisinin bu yolağın anti-absans etki açısından potansiyel bir terapötik hedef olarak değerlendirilebileceğine işaret etmektedir.

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Cite This Article

YILMAZ, N. Ç., YAVUZ, M., ERYİĞİT, T., KURT, A. H., KÜÇÜK, M. U., ONAT, F., BÜYÜKAFŞAR, K. (2019). The Role of Rho/Rho-Kinase Pathway in the Pathophysiology of Absence Epilepsy. Epilepsi, Cilt: 25 - Sayı: 1, 1–7. https://ajindex.com/articles/150780

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