Possible Anti-Inflammatory Role of Perivascular Macrophages In A Model of Depression Induced By Chronic Mild Stress In Rats

2016 ◽  
Vol 33 (S1) ◽  
pp. S525-S525
Author(s):  
A. Sayd ◽  
K. MacDowell ◽  
L. Monteagudo ◽  
D. Martin ◽  
J.L. Madrigal ◽  
...  
Keyword(s):  
Chronic Mild Stress ◽  
Prostaglandin E ◽  
Mild Stress ◽  
Mrna Levels ◽  
Protein Levels ◽  
Perivascular Macrophages ◽  
Central Nervous Systems ◽  
Anti Inflammatory ◽  
Competing Interest ◽  
Inflammatory Profile

Perivascular macrophages (PVM) are hematopoyetic cells that migrate to the brain perivascular space modulating the interactions between the immune and central nervous systems (CNS). Previously, their depletion with the icv administration of the pro-apoptotic drug clodronate encapsulated in liposomes increased the vascular production of the proinflammatory prostaglandin E2 (PGE2), the release of ACTH, corticosterone and fever, induced by the intravenous administration of Lipopolysaccharide (LPS). Further studies also demonstrated a decrease in the synthesis of the anti-inflammatory prostaglandin 15d-PGJ2.With this background, we decide to deeper explore the mechanisms involved in the anti-inflammatory profile of PVM by depleting them in a model of depression induced by chronic mild stress (CMS) exposure in rats.Our results showed an increase of the proinflammatory cytokines TNFα, IL-1 and IL-6 at mRNA levels in the prefrontal cortex of the groups of animals where the PVM were depleted, as well as in the protein levels of the pro-inflammatory nuclear factor NF-κB, the enzymatic pro-inflammatory enzymatic sources iNOS, COX-2 and m-PGES-1 and their product PGE2. A concomitant decrease of the 15d-PGJ2 mediator was also observed. In addition, we also checked whether the depletion of PVMs could regulate the expression of molecules implicated in the leukocyte traffic and infiltration in the CNS in our CMS model. Thus, the mRNA levels of the chemokines MCP-1, fractalkine and the adhesion molecule VCAM appeared increased in the animals without PVMs.In summary, our results could suggest a potential anti-inflammatory role for PVMs in a depression model chronic stress-induced as CMS.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Kyungheechunggan-Tang-01, a New Herbal Medication, Suppresses LPS-Induced Inflammatory Responses through JAK/STAT Signaling Pathway in RAW 264.7 Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Hee-Soo Han ◽  
Eungyeong Jang ◽  
Ji-Sun Shin ◽  
Kyung-Soo Inn ◽  
Jang-Hoon Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Molecular Data ◽  
Mrna Levels ◽  
Protein Levels ◽  
Stat3 Phosphorylation ◽  
Stat Signaling ◽  
Cox 2 ◽  
Anti Inflammatory

Medicinal plants have been used as alternative therapeutic tools to alleviate inflammatory diseases. The objective of this study was to evaluate anti-inflammatory properties of Kyungheechunggan-tang- (KCT-) 01, KCT-02, and Injinchunggan-tang (IJCGT) as newly developed decoctions containing 3–11 herbs in LPS-induced macrophages. KCT-01 showed the most potent inhibitory effects on LPS-induced NO, PGE2, TNF-α, and IL-6 production among those three herbal formulas. In addition, KCT-01 significantly inhibited LPS-induced iNOS and COX-2 at protein levels and expression of iNOS, COX-2, TNF-α, and IL-6 at mRNA levels. Molecular data revealed that KCT-01 attenuated the activation of JAK/STAT signaling cascade without affecting NF-κB or AP-1 activation. In ear inflammation induced by croton oil, KCT-01 significantly reduced edema, MPO activity, expression levels of iNOS and COX-2, and STAT3 phosphorylation in ear tissues. Taken together, our findings suggest that KCT-01 can downregulate the expression of proinflammatory genes by inhibiting JAK/STAT signaling pathway under inflammatory conditions. This study provides useful data for further exploration and application of KCT-01 as a potential anti-inflammatory medicine.

Chronic mild stress induces widespread decreases in thyroid hormone α1 receptor mRNA levels in brain—Reversal by imipramine

2009 ◽  
Vol 34 (2) ◽  
pp. 281-286 ◽  
Author(s):  
Edward J. Stein ◽  
Nylson G. da Silveira Filho ◽  
Danilo C. Machado ◽  
Débora C. Hipólide ◽  
Karen Barlow ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Mrna Levels ◽  
Receptor Mrna

Electroacupuncture Prevents the Depression-Like Behavior by Inhibiting the NF-κB/NLRP3 Inflammatory Pathway in Hippocampus of Mice Subjected to Chronic Mild Stress

2022 ◽  
pp. 1-9
Author(s):  
Qi Wang ◽  
Hongsheng Bi ◽  
Hongfei Huang ◽  
Yitong Wang ◽  
Lili Gong ◽  
...  
Keyword(s):  
Chronic Mild Stress ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Sucrose Preference ◽  
Receptor Protein ◽  
Mild Stress ◽  
Inflammatory Pathway ◽  
Protein Levels ◽  
Tnf Α ◽  
Immobility Time

<b><i>Background:</i></b> The precise physiological mechanisms of acupuncture in the treatment of depression are still unknown. This study aimed to observe the effects of electroacupuncture (EA) on depression-like behavior of mouse in chronic mild stress (CMS) model and explore the underlying mechanism. <b><i>Methods:</i></b> The depression model was established by using CMS method for 6 weeks. After the third week of the CMS paradigm, EA treatment was performed daily for 15 min over a period of 3 weeks. The antidepressant-like effects of EA were evaluated using the sucrose preference test and the forced swimming test (FST). The protein levels of the nuclear factor-kappa B (NF-κB), p-NF-κB, inhibitor of NF-κB, p-IκBα, NOD-like receptor protein 3, interleukin (IL)-6, IL-1β, IL-18, and tumor necrosis factor-α (TNF-α) in hippocampus of mice were detected. <b><i>Results:</i></b> Sucrose preference was decreased after 6 weeks of CMS and the effects of CMS was reversed by EA. CMS increased immobility time and decreased latency to the first immobility in the FST test, but these effects were reversed by EA. CMS-induced nuclear entry of NF-κB (nuclear/cytoplasmic ratio of NF-κB) with an increase in protein levels of p-NF-κB and p-IκBα in the hippocampus. The CMS also increased NLRP3 levels in the hippocampus. However, these effects were reversed by EA. In addition, the levels of IL-6, IL-1β, IL-18, and TNF-α in the hippocampus were increased by CMS, and these effects of stress were reversed by EA. <b><i>Conclusion:</i></b> EA prevented CMS-induced depressive-like behaviors by inhibiting NF-κB/NLRP3 inflammatory pathway.

Modulation of the Nuclear Factor (Erythroid 2-Derived)-Like 2 Pathway by Antidepressants In Rats

2016 ◽  
Vol 33 (S1) ◽  
pp. S527-S527
Author(s):  
D. Martín Hernández ◽  
Á.G. Bris ◽  
K.S. MacDowell ◽  
A. Sayd ◽  
D. Azpiazu ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Wistar Rats ◽  
Nitrosative Stress ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Nuclear Factor ◽  
Nrf2 Pathway ◽  
Antidepressant Treatments ◽  
Male Wistar Rats ◽  
Competing Interest

IntroductionPatients with major depression who are otherwise medically healthy have activated inflammatory pathways. It has been described that depression is not only escorted by inflammation but also by induction of multiple oxidative/nitrosative stress pathways. Nevertheless, there are finely regulated mechanisms involved in preserving cells from damage, such as the nuclear factor Nrf2.AimsTo explore in a depression-like model the Nrf2 pathway in the prefrontal cortex (PFC) and the hippocampus of rats and to analyze which classic antidepressants affect the antioxidant activity of the Nrf2 pathway.MethodsMale Wistar rats were exposed to chronic mild stress (CMS) and some of them were treated with desipramine, escitalopram or duloxetine. We studied the expression in the PFC and hippocampus of upstream and downstream elements of the Nrf2 pathway and the oxidative damage induced by the CMS.ResultsAfter exposure to a CMS protocol, in the PFC, there is an inhibition of upstream and downstream elements of the Nrf2 pathway. Moreover, antidepressant treatments, particularly desipramine and duloxetine, are able to recover some of these elements and to reduce the oxidative damage induced by the depression model. In the hippocampus however, Nrf2 pathways are not that affected and antidepressants do not have many actions.ConclusionsNrf2 pathway is differentially regulated by antidepressants in the PFC and hippocampus. The Nrf2 pathway is involved in the oxidative/nitrosative damage detected in the PFC after CMS exposure. However, it seems that Nrf2 is not very involved in the effects caused by the CMS in the hippocampus.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Chronic Mild Stress Modulates Activity-Dependent Transcription of BDNF in Rat Hippocampal Slices

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Raffaella Molteni ◽  
Andrea C. Rossetti ◽  
Elisa Savino ◽  
Giorgio Racagni ◽  
Francesca Calabrese
Keyword(s):  
Intracellular Signaling ◽  
Ex Vivo ◽  
Hippocampal Slices ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Mrna Levels ◽  
Bdnf Expression ◽  
Bdnf Mrna ◽  
Activity Dependent ◽  
Bdnf Transcription

Although activity-dependent transcription represents a crucial mechanism for long-lasting experience-dependent changes in the hippocampus, limited data exist on its contribution to pathological conditions. We aim to investigate the influence of chronic stress on the activity-dependent transcription of brain-derived neurotrophic factor (BDNF). Theex vivomethodology of acute stimulation of hippocampal slices obtained from rats exposed to chronic mild stress (CMS) was used to evaluate whether the adverse experience may alter activity-dependent BDNF gene expression. CMS reduces BDNF expression and that acute depolarization significantly upregulates total BDNF mRNA levels only in control animals, showing that CMS exposure may alter BDNF transcription under basal conditions and during neuronal activation. Moreover, while the basal effect of CMS on total BDNF reflects parallel modulations of all the transcripts examined, isoform-specific changes were found after depolarization. This different effect was also observed in the activation of intracellular signaling pathways related to the neurotrophin. In conclusion, our study discloses a functional alteration of BDNF transcription as a consequence of stress. Being the activity-regulated transcription a critical process in synaptic and neuronal plasticity, the different regulation of individual BDNF promoters may contribute to long-lasting changes, which are fundamental for the vulnerability of the hippocampus to stress-related diseases.

scholarly journals Baicalin-Induced Autophagy Preserved LPS-Stimulated Intestinal Cells from Inflammation and Alterations of Paracellular Permeability

2021 ◽  
Vol 22 (5) ◽  
pp. 2315
Author(s):  
Valentina Rizzo ◽  
Nadia Ferlazzo ◽  
Monica Currò ◽  
Gaetano Isola ◽  
Marco Matarese ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Paracellular Permeability ◽  
Autophagic Flux ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Inflammatory Conditions ◽  
Anti Inflammatory

Several studies have demonstrated a relevant role of intestinal epithelial cells in the immune response and in chronic inflammatory conditions, including ulcers, colitis, and Crohn’s disease. Baicalin (BA), extracted from the root of Scutellaria baicalensis, has various beneficial healthy effects, including anti-inflammatory activity. However, few studies have evaluated BA effects on autophagic signaling in epithelial cell response to inflammatory stimuli. To explore possible beneficial effects of BA, HT-29 cells were exposed to lipopolysaccharide (LPS), in presence or absence of BA, for 4 h. We evaluated mRNA levels of autophagy-related genes and cytokines, triggering inflammatory response. Furthermore, the expression of claudin 1, involved in the regulation of paracellular permeability was analyzed. BA treatment repressed LPS-induced expression of TNF-α and IL-1β. The down-regulation of autophagy-related genes induced by LPS was counteracted by cell pretreatment with BA. Under these conditions, BA reduced the NF-κB activation caused by LPS. Also, BA restored mRNA and protein levels of claudin 1, which were reduced by LPS. In conclusion, in intestinal epithelial cells BA regulates the NF-κB activation and modulates both autophagic and inflammatory processes, leading to an improvement of paracellular permeability. These results suggest that the anti-inflammatory effects of BA can be associated to the regulation of autophagic flux.

scholarly journals Chronic Mild Stress Modified Epigenetic Mechanisms Leading to Accelerated Senescence and Impaired Cognitive Performance in Mice

2020 ◽  
Author(s):  
Dolors Puigoriol-Illamola ◽  
Mirna Martínez-Damas ◽  
Christian Griñán-Ferré ◽  
Mercè Pallàs
Keyword(s):  
Cognitive Performance ◽  
Posttranslational Modifications ◽  
Healthy Aging ◽  
Glycogen Synthase ◽  
Chronic Mild Stress ◽  
Modern Society ◽  
Public Healthcare ◽  
Mild Stress ◽  
Epigenetic Mechanisms ◽  
Protein Levels

Cognitive and behavioural disturbances are growing public healthcare issue for the modern society, as stressful lifestyle is becoming more and more common. Besides, several pieces of evidence state that environment is crucial in the development of several diseases as well as compromising healthy aging. Therefore, it is important to study the effects of stress on cognition and its relationship with aging. To address these queries, Chronic Mild Stress (CMS) paradigm was used in the senescence-accelerated mouse prone 8 (SAMP8) and resistant 1 (SAMR1). On one hand, we determined the changes produced in the three main epigenetic marks after 4 weeks of CMS treatment, such as a reduction in histone posttranslational modifications and DNA methylation, and up-regulation or down-regulation of several miRNA involved in different cellular processes in mice. In addition, CMS treatment induced reactive oxygen species (ROS) accumulation and loss of antioxidant defence mechanisms, as well as inflammatory signalling activation through NF-&kappa;B pathway and astrogliosis markers, like Gfap. Remarkably, CMS altered mTORC1 signalling in both strains, decreasing autophagy only in SAMR1 mice. We found a decrease in glycogen synthase kinase 3 &beta; (GSK-3&beta;) inactivation, hyperphosphorylation of Tau and an increase in sAPP&beta; protein levels in mice under CMS. Moreover, reduction in the non-amyloidogenic secretase ADAM10 protein levels was found in SAMR1 CMS group. Consequently, detrimental effects on behaviour and cognitive performance were detected in CMS treated mice, affecting mainly SAMR1 mice, promoting a turning to SAMP8 phenotype. In conclusion, CMS is a feasible intervention to understand the influence of stress on epigenetic mechanisms underlying cognition and accelerating senescence.

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