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

Dilara Nemutlu Samur; Erkan Maytalman; Öykü Zorlu

Article Details

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

Authors:

Dilara Nemutlu Samur | Erkan Maytalman | Öykü Zorlu

Publisher:

Eskişehir Osmangazi University

Main Topics:

Tıbbi Farmakoloji

Journal:

Osmangazi Tıp Dergisi Vol.47 Issue 5, pp.743-750

Document Type:

Article

Publication Date:

4/2025

Document Language:

English

Document ID (Org No.):

2001341762

pISSN:

1305-4953

Keywords:

Abstract:

 Parkinsons 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 TLR4NF-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 TLR4NF-κB pathways and could be investigated as a potential therapeutic compound in inflammation-based models of the gut-brain axis in PD.

 Parkinsons 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 TLR4NF-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 TLR4NF-κB pathways and could be investigated as a potential therapeutic compound in inflammation-based models of the gut-brain axis in PD.

 Parkinsons 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 TLR4NF-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 TLR4NF-κB pathways and could be investigated as a potential therapeutic compound in inflammation-based models of the gut-brain axis in PD.

 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 TLR4NF-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 TLR4NF-κB yolakları üzerinden inflamatuvar yanıtı düzenleyebileceğini ve PHnin bağırsak-beyin eksenine dayalı inflamasyon modelinde potansiyel bir terapötik madde olarak çalışılabileceğini göstermektedir.

Article Details

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

Authors:

Dilara Nemutlu Samur | Erkan Maytalman | Öykü Zorlu

Publisher:

Eskişehir Osmangazi University

Main Topics:

Tıbbi Farmakoloji

Journal:

Osmangazi Tıp Dergisi Vol.47 Issue 5, pp.743-750

Document Type:

Article

Publication Date:

4/2025

Document Language:

English

Document ID (Org No.):

2001341762

pISSN:

1305-4953

Enteric inflammation

Enteric glia

Rotenone

Toll-like receptor

VortioxetineEnterik inflamasyon

Enterik glia

Rotenon

Toll-benzeri reseptör

Vortioksetin.

Issues

Article Details

Authors: Dilara Nemutlu Samur | Erkan Maytalman | Öykü Zorlu

Publisher: Eskişehir Osmangazi University

Main Topics: Tıbbi Farmakoloji

Journal: Osmangazi Tıp Dergisi Vol.47 Issue 5, pp.743-750

Document Type: Article

Publication Date: 4/2025

Document Language: English

Document ID (Org No.): 2001341762

pISSN: 1305-4953

Issues

Authors:

Dilara Nemutlu Samur | Erkan Maytalman | Öykü Zorlu

Publisher:

Eskişehir Osmangazi University

Main Topics:

Tıbbi Farmakoloji

Journal:

Osmangazi Tıp Dergisi Vol.47 Issue 5, pp.743-750

Document Type:

Article

Publication Date:

4/2025

Document Language:

English

Document ID (Org No.):

2001341762

pISSN:

1305-4953