P.836 The effects of agmatine by chronic unpredictable mild stress-induced depression in rats: Involvement of neuroinflammation through toll-like receptor-4

2019 ◽  
Vol 29 ◽  
pp. S556
Author(s):  
F. Aricioglu ◽  
T. Utkan
2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
Hongfeng Gu ◽  
Chaoke Tang ◽  
Kuang Peng ◽  
Hui Sun ◽  
Yongzong Yang

Here, we investigated the effect of chronic mild stress (CMS) on the development of atherosclerosis as well as the expression of Toll-like receptors (TLRs) signaling pathway in adolescent apolipoprotein E knockout (apoE-/-) mice. Mice were subjected to daily CMS for 0, 4, and 12 weeks, respectively. To identify the expression of Toll-like receptor 4 signaling pathway in adolescent apolipoprotein E knockout mice subjected to CMS, we compared gene expression in aortas of stressed and unstressed mice using TLRs signaling pathway real-time PCR microarrays consisting of 87 genes. We found that atherosclerosis lesions both in aortic tress and sinuses of CMS mice were significantly increased linearly in response to duration of CMS exposure. Among 87 genes analyzed, 15 genes were upregulated in stressed mice, especially TLR4, myeloid differentiation factor 88 (MyD88), and IL-1β, and 28 genes were downregulated compared with nonstressed mice. CMS mice demonstrated markedly increased aortic atherosclerosis that were associated with significant increases in levels of expression of TLR4, MyD88, nuclear factorκB (NF-κB), MCP-1, IL-1β, TNF-α, and sICAM-1. Taken together, our results suggest an important role for TLR4 signaling pathway in atherosclerosis in a CMS mouse model.


2021 ◽  
Author(s):  
Li Miao ◽  
Fei Huang ◽  
Wei Jiang ◽  
Ying-ying Sun ◽  
Yong-jin Chen ◽  
...  

Abstract BackgroundDepression, one of the most frequently-occurring psychiatric disorders worldwide, is a significant inflammatory disorder. The polyphenol curcumin (Cur), which is extracted from Curcuma longa, has marked anti-inflammatory and anti‑oxidative effects against inflammatory diseases. However, whether Cur has antidepressant effects and the possible mechanisms, are unclear. The present study aimed to assess Cur’s beneficial effects on depressive-like behaviors using a chronic unpredictable mild stress (CUMS) model and its possible molecular mechanisms. MethodsWe performed CUMS treated Sprague Dawley (SD) rats as a model of depression. Behavioral observations were performed by sucrose preference test (SPT), force swimming test (FST) and tail suspension test (TST). Hippocampal expression of oxidative stress markers and inflammatory cytokines were measured with ELISA. Hippocampal expression of high-mobility group box 1 (HMGB1), IL-1β, TNF-α and IL-6 were determined with quantitative PCR analyses and immunofluorescent staining. Hippocampal Toll-like receptor 4 (TLR4) and NF-κB activation were examined with Western blotting analysis.ResultsRats subjected to CUMS demonstrated marked depressive-like behavior (decreased locomotor activity and sucrose intake, and prolonged immobility). Their levels of oxidative stress and inflammatory cytokines increased significantly, and their levels of phosphorylated nuclear factor kappa-B (NF-κB), toll-like receptor 4 (TLR4), and HMGB1, also increased in the hippocampus. The changes were ameliorated significantly by treatment with Cur (50, 100 mg/kg) to varying degrees.Conclusion This study demonstrated that Cur has a potent antidepressant effect via the HMGB1/TLR4/NF-κB pathway, suggesting that Cur might be a promising therapeutic drug for depression.


2007 ◽  
Vol 6 (1) ◽  
pp. 142-143
Author(s):  
A RIAD ◽  
S BIEN ◽  
M GRATZ ◽  
S BERESWILL ◽  
H SCHULTHEISS ◽  
...  

VASA ◽  
2014 ◽  
Vol 43 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Tao Shang ◽  
Feng Ran ◽  
Qian Qiao ◽  
Zhao Liu ◽  
Chang-Jian Liu

Background: The purpose of this study was to determine whether myeloid differentiation factor88-dependent Toll-Like Receptor-4 (TLR-4) signaling contributed to the inhibition of abdominal aortic aneurysm (AAA) by Tanshinone IIA (Tan IIA). Materials and methods: Male Sprague-Dawley rats (n = 12 / group) were randomly distributed into three groups: Tan IIA, control, and sham. The rats from Tan IIA and control groups under-went intra-aortic elastase perfusion to induce AAAs, and those in the sham group were perfused with saline. Only the Tan IIA group received Tan IIA (2 mg / rat / d). Aortic tissue samples were harvested at 24 d after perfusion and evaluated using reverse transcriptase-polymerase chain reaction, Western blot, immunohistochemistry and immunofluorescence. Results: The over-expression of Toll-Like Receptor-4 (TLR-4), Myeloid Differentiation factor 88 (MyD88), Phosphorylated Nuclear Factor κB (pNF-κB) and Phosphorylated IκBα (pIκBα) induced by elastase perfusion were significantly decreased by Tan IIA treatment. Conclusions: Tan IIA attenuates elastase-induced AAA in rats possibly via the inhibition of MyD88-dependent TLR-4 signaling, which may be one potential explanation of why Tan IIA inhibits AAA development through multiple effects.


2020 ◽  
Vol 41 (2) ◽  
pp. 134-140
Author(s):  
Yuriy Bisyuk ◽  
Andrew Dubovyi ◽  
Ilona DuBuske ◽  
Viktor Litus ◽  
Lawrence M. DuBuske

Background: This study assessed gene polymorphisms of the CD14 receptor (C-159T) and Toll-like receptor 4 (Asp299Gly) in a patient population in Crimea, Ukraine, stratified by clinical (early versus late onset; frequent versus occasional relapses; fixed versus reversible obstruction) and immunologic (atopic versus nonatopic; eosinophilic; neutrophilic or paucigranulocytic inflammation) subtype. Methods: Two polymorphisms, CD14 C-159T and TLR4 Asp299Gly, were assessed in 331 patients with asthma. The control group included 285 volunteers who were nonatopic. The single nucleotide polymorphisms were studied by using polymerase chain reaction with electrophoretic detection. Results: There were increased odds of asthma development in patients with the Asp299Gly TLR4 mutation compared with the general population underdominant odds ratio (OR) 1.52 [95% confidence interval (CI), 1.00‐2.32] and overdominant (OR 1.55 [95% CI, 1.01‐2.38]) models after adjustment for gender and age. In addition, mutations in this gene decreased the odds of nonatopic asthma in underdominant (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.027), overdominant (OR 0.27 [95% CI, 0.07‐0.96]; p = 0.033), and log-additive models (OR 0.26 [95% CI, 0.07‐0.93]; p = 0.026) compared with the atopic subgroup after adjustment for gender, age, number of exacerbations, and type of airway inflammation. Allele frequencies for CD14 and TLR4 polymorphisms did not show statistical differences between the patients with asthma and the control subjects. Conclusion: CD14 C-159T polymorphisms were not associated with asthma in the adult population in Crimea. TLR4 Asp299Gly polymorphisms were associated with asthma and with decreased odds of nonatopic asthma compared with atopic asthma in the adult population in Crimea.


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