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Yıl:2023; Cilt: 26; Sayı: 4>> Özet
TAM METİN
Klinik Psikiyatri Dergisi; 2023;26(4):238-247
Sıçanlarda kronik hafif strese bağlı depresyonda antidepresan tedavisinin hipokampus ve hipotalamus endoplazmik retikulum stresi üzerine etkilerinin araştırılması
M Karaağaç, M Ak, E Kurar, F Uguz, S Kutlu
Karaman Eğitim ve Araştırma Hastanesi, Karaman
GİRİŞ ve AMAÇ: Bu çalışmada, kronik hafif stres modeline maruz bırakılan dişi sıçanlarda endoplazmik retikulum (ER) stresinin depresyon patofizyolojisindeki rolünün incelenmeyi amaçlanmıştır YÖNTEM ve GEREÇLER: 48 dişi erişkin ratta kronik hafif stres modeli oluşturuldu ve kontrol, depresyon, depresyon+1 mg/kg sertralin ve depresyon+10 mg/kg sertralin olmak üzere 4 gruba ayrıldı. Ozmotik mini pompalar kullanılarak 14 gün boyunca deri altı ilaç infüzyonları gerçekleştirildi. Sıçanların hipotalamus ve hipokampus dokularında ER stres yolundaki genlerin ekspresyon düzeyleri değerlendirildi. BULGULAR: ATF4 gen ekspresyonunun hipokampusta depresyonda arttığı ve tedavi ile azaldığı saptandı. Hipokampal GRP78 gen ekspresyonu, tedaviden sonra aşağı regüle edildi. Hipotalamik ve hipokampal CALR gen ekspresyonu tedavi ile azaldı ve hipotalamik HSP47 gen ekspresyonu her iki tedavi grubunda da azaldı. Hipotalamik ve hipokampal XPB1 gen ekspresyonu tedavi ile azaldı ve hipokampal XPB1 gen ekspresyonu depresyon +1 mg/kg sertralin grubuna kıyasla depresyon +10 mg/kg sertralin grubunda daha da fazla azaldı TARTIŞMA ve SONUÇ: Bu bulgular ER stres mekanizmasının depresyon patofizyolojisinde rol oynayabileceğini ve bu mekanizmanın tedavi ile tersine çevrilebileceğini göstermektedir. Çalışmamızın sonuçları insan çalışmaları için cesaret verici olmuş ve antidepresan etkinin anlaşılması ve hızlandırılması için yeni projelerin önünü açmıştır.
Investigation of the effects of antidepressant treatment on hippocampus and hypothalamus endoplasmic reticulum stress in chronic mild stress induced depression in rats
Objective: This study aimed to examine the role of endoplasmic reticulum (ER) stress in the pathophysiology of depression in female rats exposed to the chronic mild stress model. Method: Chronic mild stress model was constituted in 48 female adult rats were and divided into 4 groups as control, depression, depression+1 mg/kg sertraline, and depression+10 mg/kg sertraline. Subcutaneous drug infusions were performed for 14 days using osmotic minipumps. Expression levels of genes in ER stress pathway were evalulated in hypothalamus and hippocampus tissues of rats. Results: It was found that ATF4 gene expression increased in depression in the hippocampus and decreased with treatment. Hippocampal GRP78 gene expression was downregulated after treatment. Hypothalamic and hippocampal CALR gene expression decreased with treatment, hypothalamic HSP47 gene expression decreased in both treatment groups. Hypothalamic and hippocampal XPB1 gene expression decreased with treatment, hippocampal XPB1 gene expression was further downregulated in the depression +10 mg/kg sertraline group compared to the depression+1 mg/kg sertraline group. Discussion: These findings show that the ER stress mechanism may have a role in the pathophysiology of depression and that this mechanism can be reversed with treatment. The results of our study have been encouraging for human studies and open the way for new projects to understand and accelerate the antidepressant effect.

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