Elektrokonvülsif terapinin Sıçan Depresyon Modelinde hipokampal endoplazmik retikulum stresi üzerine etkisi
Küçük Resim Yok
Tarih
2023
Yazarlar
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Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Depresyonun en etkili tedavilerden biri olan elektrokonvülsif tedavinin (EKT), etkinliğinin altında yatan mekanizmalar halen bilinmemektedir. Depresyonda artan ER stresi farmakolojik ajanlarla geriye çevirebilirken EKT'nin bu konudaki etkinliği henüz incelenmemiştir. Bu çalışmada, sıçan depresyon modelinde tekrarlanan EKT'den sonra hipokampal ER stres parametrelerinin nasıl değiştiğini test ettik. Materyal ve metot: Sıçanlar 4 gruba ayrılmıştır. Deney grubunda yer alan 2 gruba 21 gün boyunca kronik öngörülemeyen hafif stresin modelini (CUMS) kullanılarak deneysel depresyon modeli oluşturulmaya çalışılmıştır. Daha sonra bir deney ve bir kontrol grubundan olmak üzere 2 gruba 21 gün boyunca deneysel EKT modeli uygulanmıştır. Kilo değişimleri ve Zorlu Yüzme Testine (ZYT) sonuçları 21. ve 42. günün sonunda değerlendirilmiştir. Son aşamada çıkarılan hipokampusta Western Blot ile ER stresi ile ilgili üç belirgin protein (Grp-78, Xbp1 ve Atf-4) ölçülmüştür. Bulgular: CUMS uygulanan sıçanların, ZYT'de beklenen artmış hareketsizlik süresi tam olarak oluşmasa da kilo kaybı gibi depresyon benzeri davranış tepkileri sergilediğini bulduk. CUMS uygulanan sıçanlarda Grp-78 düzeyleri artarken, Atf-4 düzeyleri değişmedi, Xbp1 düzeyleri ise azaldı. EKT normal sıçanlarda Grp-78 düzeylerini artırırken, Atf-4 düzeyleri değiştirmedi ve Xbp1 düzeylerini azalttı. Depresyon modeli uygulanan sıçanlarda ise EKT ile artan Grp-78 düzeyleri azalırken Atf-4 düzeyleri değişmedi, Xbp1 düzeylerini ise azaldı. Sonuç: Bu bulgular artan ER stresin depresyon patofizyolojisinde rol oynayabileceğini ve bu artışın EKT tedavi ile tersine çevrilebileceğini göstermektedir. Bu bulguların insanlarda yapılacak klinik çalışmalarla doğrulanması gerekir. Anahtar kelimeler: Depresyon, EKT, Endoplazmik Retikulum Stresi
Aim: The mechanisms underlying the effectiveness of electroconvulsive therapy (ECT), one of the most effective treatments for depression, are still unknown. While the increasing ER stress in depression can retrieve with pharmacological agents, ECT's effectiveness has not been examined yet. In this study, we tested how hippocampal ER stress parameters changed after the repeated ECT in the rats depression model. Material and Method: Rats were divided into 4 groups. An experimental depression model was tried to be created for 2 groups in the experimental group using the chronic unpredictable mild stress model (CUMS) for 21 days. Then, the experimental ECT model was applied to two groups, one experimental and one control group, for 21 days. Weight changes and Forced Swimming Test (FST) results were evaluated at the end of the 21st and 42nd day. In the final step, three prominent ER stress-related proteins (Grp-78, Xbp1, and Atf-4) were measured by Western Blot in the removed hippocampus. Results: We found that rats administered CUMS exhibited depression-like behavioral responses such as weight loss, although the increased immobility time expected in FST did not fully occur. In CUMS-treated rats, Grp-78 levels increased, Atf-4 levels did not change, and Xbp1 levels decreased. While ECT increased Grp-78 levels in normal rats, it did not change Atf-4 levels and reduced Xbp1 levels. In rats treated with depression model, Grp-78 levels, which increased with ECT, decreased, Atf-4 levels did not change, and Xbp1 levels decreased. Conclusion: These findings show that increased ER stress may play a role in the pathophysiology of depression and that this increase can be reversed with ECT treatment. These findings need to be confirmed by clinical studies in humans. Key words: Depression, ECT, Endoplasmic Reticulum Stress
Aim: The mechanisms underlying the effectiveness of electroconvulsive therapy (ECT), one of the most effective treatments for depression, are still unknown. While the increasing ER stress in depression can retrieve with pharmacological agents, ECT's effectiveness has not been examined yet. In this study, we tested how hippocampal ER stress parameters changed after the repeated ECT in the rats depression model. Material and Method: Rats were divided into 4 groups. An experimental depression model was tried to be created for 2 groups in the experimental group using the chronic unpredictable mild stress model (CUMS) for 21 days. Then, the experimental ECT model was applied to two groups, one experimental and one control group, for 21 days. Weight changes and Forced Swimming Test (FST) results were evaluated at the end of the 21st and 42nd day. In the final step, three prominent ER stress-related proteins (Grp-78, Xbp1, and Atf-4) were measured by Western Blot in the removed hippocampus. Results: We found that rats administered CUMS exhibited depression-like behavioral responses such as weight loss, although the increased immobility time expected in FST did not fully occur. In CUMS-treated rats, Grp-78 levels increased, Atf-4 levels did not change, and Xbp1 levels decreased. While ECT increased Grp-78 levels in normal rats, it did not change Atf-4 levels and reduced Xbp1 levels. In rats treated with depression model, Grp-78 levels, which increased with ECT, decreased, Atf-4 levels did not change, and Xbp1 levels decreased. Conclusion: These findings show that increased ER stress may play a role in the pathophysiology of depression and that this increase can be reversed with ECT treatment. These findings need to be confirmed by clinical studies in humans. Key words: Depression, ECT, Endoplasmic Reticulum Stress
Açıklama
Anahtar Kelimeler
Fizyoloji, Physiology, Genetik
