Sıçan Kökenli Enteroglial Hücrelerde Rotenon ile İndüklenen İnflamatuvar Değişiklikler Üzerine Vortioksetinin Etkileri: TLR4/NFκB Sinyal Yolağının Rolü

Yıl 2025, Cilt: 47 Sayı: 5, 743 - 750, 04.09.2025

Dilara Nemutlu Samur , Erkan Maytalman , Öykü Zorlu

https://doi.org/10.20515/otd.1672924

Öz

Parkinson hastalığı (PH) progresif bir nörodejeneratif hastalık olup günümüzde hastalığı durdurmaya yönelik kesin bir tedavi seçeneği bulunmamaktadır. Gastrointestinal inflamasyon, PH ile ilişkili motor-olmayan bulgulardan biridir. Son yıllarda antidepresanların potansiyel antiinflamatuvar etkileri nedeniyle nörodejeneratif hastalıkların tedavisinde kullanılabileceğine dair ilgi artmıştır. Bu çalışmada, vortioksetinin enterik glia hücrelerinde rotenon ile indüklenen inflamatuvar yanıtlar üzerindeki etkisi ve bu etkisinde TLR4/NF-κB sinyal yolağının rolü araştırılmıştır. Rotenon (10 μM) ve vortioksetin (1 ve 5 μM) ile muamele edilmiş hücre örneklerinde TLR4 ve NF-κB mRNA ekspresyonları RT-qPCR ile, TNF-α, IL-1β ve IL-6 düzeyleri ise ELISA yöntemiyle değerlendirilmiştir. Bulgular, rotenonun glial hücrelerin immün yanıtlarını bozarak TLR4 ve NF-κB ekspresyonunu belirgin şekilde baskıladığını ve bu etkinin 5 μM vortioksetin uygulamasıyla daha da arttığını göstermiştir. Ayrıca rotenon gruplarında TNF-α ve IL-1β düzeylerinde gözlenen düşüş, vortioksetin uygulaması ile tersine dönmüştür. Sonuçlar, vortioksetinin enterik glia hücrelerinde TLR4/NF-κB yolakları üzerinden inflamatuvar yanıtı düzenleyebileceğini ve PH’nin bağırsak-beyin eksenine dayalı inflamasyon modelinde potansiyel bir terapötik madde olarak çalışılabileceğini göstermektedir.

Anahtar Kelimeler

Enterik inflamasyon , Enterik glia , Rotenon , Toll-benzeri reseptör , Vortioksetin.

Proje Numarası

1919B012209240

The Effects of Vortioxetine on Rotenone-Induced Inflammatory Changes in Rat-Derived Enteroglial Cells: The Role of the TLR4/NFκB Signaling Pathway

Öz

Parkinson’s disease (PD) is a progressive neurodegenerative disorder with both motor and non-motor symptoms, and currently, there is currently no disease-modifying therapy. Due to their potential anti-inflammatory effects, antidepressants have gained attention as therapeutic agents in inflammation-related neurological conditions. In this study, we aimed to investigate the effects of vortioxetine on rotenone-induced enteric inflammation in an in vitro model using enteric glial cells and whether these effects involve modulation of the TLR4/NF-κB signaling pathway. Cells were treated with rotenone (10 μM) and vortioxetine (1 and 5 μM). TLR4 and NF-κB mRNA expression levels were analyzed by RT-qPCR, and the levels of TNF-α, IL-1β, and IL-6 were measured via ELISA. The findings showed that rotenone significantly suppressed TLR4 and NF-κB expression by impairing the immune responses of glial cells, and the administration of 5 μM vortioxetine further enhanced this effect. Additionally, the decrease observed in TNF-α and IL-1β levels in the rotenone groups was reversed by vortioxetine administration. The results suggest that vortioxetine may regulate inflammatory responses in enteric glial cells through the TLR4/NF-κB pathways and could be investigated as a potential therapeutic compound in inflammation-based models of the gut-brain axis in PD.

Anahtar Kelimeler

Enteric inflammation , Enteric glia , Rotenone , Toll-like receptor , Vortioxetine

Etik Beyan

None

Destekleyen Kurum

TÜBİTAK (The Scientific and Technological Research Council of Turkey)

Proje Numarası

1919B012209240

Teşekkür

This work was supported by grants from the Scientific and Technological Research Council of Turkey, TÜBİTAK (2209-A - Research Project Support Programme for Undergraduate Students, Application number: 1919B012209240). The authors would like to express their appreciation to Lundbeck A/S for supplying vortioxetine for research purposes. We also extend our thanks to Dr. Luca Antonioli for providing the enteroglial cell line that was used in this study.

Kaynakça

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