Publication: Genetik absans epilepsili sıçanlarda aralıklı açlığın nörogenez üzerine etkilerinin cinsiyet farklılığı açısından incelenmesi
Abstract
Amaç Bu çalışma, aralıklı açlık (AA) ve nörogenez arasındaki patofizyolojik mekanizmaları, cinsiyet farklılığı açısından değerlendirerek araştırmayı amaçlamaktadır. Gereç ve Yöntem: Çalışmada 28 dişi ve 28 erkek sıçan dörder gruba ayrılmıştır: Wistar Kontrol (WK), Wistar + aralıklı açlık (WAA), GAERS + kontrol (GK), GAERS + aralıklı açlık (GAA). Sıçanlara pasif sakınma ve açık alan testleri uygulanmış, beyin ve kolon dokuları histopatolojik olarak değerlendirilmiştir. Nörogenezi incelemek için beyin dokusunda DCX ve KB proteinleri immünohistokimya (İHK) ve western blot (WB) yöntemleri ile, doku bütünlüğünü göstermek için kolon dokusunda okludin proteini İHK yöntemiyle incelenmiştir. Her iki dokuda da oksidatif stres belirteçleri, ELISA yöntemiyle ölçülmüştür. Bulgular: GAERS sıçanların EEG analizinde, AA grubu sıçanların ortalama nöbet süresi, kontrol grubuna göre azalma eğilimi göstermiştir. Pasif sakınma testinde geçiş gecikmesi, GK grubunda tüm deney gruplarına göre bir düşüş sergilerken, GAA grubunda bu düşüş anlamlı olarak artmıştır (p<0.001). Açık alan testinde, WK grubuna göre WAA grubunda anlamlı derecede artan dolaşma mesafesi gözlenirken (p<0,01), GAERS sıçanlarda fark izlenmemiştir. İHK ve WB sonuçlarına göre, DCX ve KB ekspresyonlarında Wistar-Kontrol ve Wistar-AA arasında bir fark göstermezken; GAA grubunda, GK grubuna kıyasla anlamlı düzeyde artmıştır. Kolon histopatolojisinde GAA grubunda, GK grubuna göre artan hasar skoru ve goblet hücre sayısı (p<0,01, p<0,001,p<0,0001) belirlendi. GAERS gruplarındaki azalmış okludin ekspresyonu, AA uygulamasıyla anlamlı derecede arttı (p<0,05, p<0,01). Beyin örneklerinde MPO, MDA değerlerinde anlamlı bir fark gözlenmezken, kolon dokusunda erkek gruplarda MDA seviyesinin GK gruplarda epileptik erkek hayvanlarda anlamlı bir şekilde arttı (p<0,05). GSH, SOD ve KAT düzeylerinin hem beyin hem kolon dokularında, her iki cinsiyette GAA gruplarında GK grubuna göre anlamlı şekilde yüksek olduğu bulundu (p<0,05, p<0,01, p<0,001). Sonuç: Çalışmamızın verileri AA'nın epilepsi üzerindeki olası yararlı etkilerini, nörogenez ve bağırsak-beyin ekseni üzerinden gösterdiğini düşündürmektedir. Bu mekanizmanın aydınlatılması için ileride yapılacak çalışmalara ihtiyaç vardır.
Objective: This study aims to investigate the pathophysiological mechanisms linking epilepsy, intermittent fasting (AA), and neurogenesis with a focus on gender differences. Materials and Methods: In this study, a total of 28 female and 28 male rats were divided into four groups: Wistar Control (WK), Wistar + Intermittent Fasting (WAA), GAERS + Control (GK), and GAERS + Intermittent Fasting (GAA). The rats underwent passive avoidance and open field tests, and their brain and colon tissues were histopathologically evaluated. To examine neurogenesis, DCX and KB proteins in brain tissue were analyzed using immunohistochemistry (IHC) and western blot (WB) methods. To assess tissue integrity, occludin protein in colon tissue was examined using the IHC method. Oxidative stress markers were measured using the ELISA method. Results: In EEG analysis, the AA group showed a decreasing trend in seizure duration compared to the control. In the passive avoidance test, transition latency decreased in the GK group, whereas it significantly increased in the GAA group (p<0.001). In the open field test, locomotion distance was significantly higher in the WAA group compared to the WK group (p<0.01), with no difference in GAERS rats. IHC and WB analyses revealed no differences in DCX and KB expression between the Wistar-Control and Wistar-AA groups, but a significant increase in the GAA group compared to the GK group. Colon histopathology showed higher scores and goblet cell counts in the GAA group than in the GK group (p<0.01, p<0.001, p<0.0001). Occludin expression, reduced in GAERS groups, significantly increased with AA treatment (p<0.05, p<0.01). While MPO and MDA levels in brain tissue showed no differences, kidney MDA levels were higher in male GK rats (p<0.05). GSH, SOD, and CAT levels were significantly elevated in the GAA group in both brain and colon tissues (p<0.05, p<0.01, p<0.001). Conclusion: The data from our study suggest that intermittent fasting may have beneficial effects on epilepsy via neurogenesis and the gut-brain axis.
Objective: This study aims to investigate the pathophysiological mechanisms linking epilepsy, intermittent fasting (AA), and neurogenesis with a focus on gender differences. Materials and Methods: In this study, a total of 28 female and 28 male rats were divided into four groups: Wistar Control (WK), Wistar + Intermittent Fasting (WAA), GAERS + Control (GK), and GAERS + Intermittent Fasting (GAA). The rats underwent passive avoidance and open field tests, and their brain and colon tissues were histopathologically evaluated. To examine neurogenesis, DCX and KB proteins in brain tissue were analyzed using immunohistochemistry (IHC) and western blot (WB) methods. To assess tissue integrity, occludin protein in colon tissue was examined using the IHC method. Oxidative stress markers were measured using the ELISA method. Results: In EEG analysis, the AA group showed a decreasing trend in seizure duration compared to the control. In the passive avoidance test, transition latency decreased in the GK group, whereas it significantly increased in the GAA group (p<0.001). In the open field test, locomotion distance was significantly higher in the WAA group compared to the WK group (p<0.01), with no difference in GAERS rats. IHC and WB analyses revealed no differences in DCX and KB expression between the Wistar-Control and Wistar-AA groups, but a significant increase in the GAA group compared to the GK group. Colon histopathology showed higher scores and goblet cell counts in the GAA group than in the GK group (p<0.01, p<0.001, p<0.0001). Occludin expression, reduced in GAERS groups, significantly increased with AA treatment (p<0.05, p<0.01). While MPO and MDA levels in brain tissue showed no differences, kidney MDA levels were higher in male GK rats (p<0.05). GSH, SOD, and CAT levels were significantly elevated in the GAA group in both brain and colon tissues (p<0.05, p<0.01, p<0.001). Conclusion: The data from our study suggest that intermittent fasting may have beneficial effects on epilepsy via neurogenesis and the gut-brain axis.