scholarly journals A new experimental design to study inflammation-related versus non-inflammation-related depression in mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Pierre Cardinal ◽  
Camille Monchaux de Oliveira ◽  
Julie Sauvant ◽  
Aline Foury ◽  
Muriel Darnaudéry ◽  
...  
Keyword(s):  
Experimental Design ◽  
Chronic Mild Stress ◽  
Health Concern ◽  
Inflammatory Factors ◽  
Mild Stress ◽  
Activation Markers ◽  
Relative Contribution ◽  
Inflammatory Conditions ◽  
Dopaminergic Systems ◽  
Serotoninergic And Dopaminergic Systems

Abstract Background Major depressive disorder (MDD) represents a major public health concern, particularly due to its steadily rising prevalence and the poor responsiveness to standard antidepressants notably in patients afflicted with chronic inflammatory conditions, such as obesity. This highlights the need to improve current therapeutic strategies, including by targeting inflammation based on its role in the pathophysiology and treatment responsiveness of MDD. Nevertheless, dissecting the relative contribution of inflammation in the development and treatment of MDD remains a major issue, further complicated by the lack of preclinical depression models suitable to experimentally dissociate inflammation-related vs. inflammation-unrelated depression. Methods While current models usually focus on one particular MDD risk factor, we compared in male C57BL/6J mice the behavioral, inflammatory and neurobiological impact of chronic exposure to high-fat diet (HFD), a procedure known to induce inflammation-related depressive-like behaviors, and unpredictable chronic mild stress (UCMS), a stress-induced depression model notably renowned for its responsivity to antidepressants. Results While both paradigms induced neurovegetative, depressive-like and anxiety-like behaviors, inflammation and downstream neurobiological pathways contributing to inflammation-driven depression were specifically activated in HFD mice, as revealed by increased circulating levels of inflammatory factors, as well as brain expression of microglial activation markers and enzymes from the kynurenine and tetrahydrobiopterin (BH4) pathways. In addition, serotoninergic and dopaminergic systems were differentially impacted, depending on the experimental condition. Conclusions These data validate an experimental design suitable to deeply study the mechanisms underlying inflammation-driven depression comparatively to non-inflammatory depression. This design could help to better understand the pathophysiology of treatment resistant depression.

Sodium Butyrate Functions as an Antidepressant and Improves Cognition with Enhanced Neurotrophic Expression in Models of Maternal Deprivation and Chronic Mild Stress

2014 ◽  
Vol 11 (4) ◽  
pp. 359-366 ◽  
Author(s):  
Samira Valvassori ◽  
Roger Varela ◽  
Camila Arent ◽  
Gustavo Dal-Pont ◽  
Tamara Bobsin ◽  
...  
Keyword(s):  
Sodium Butyrate ◽  
Chronic Mild Stress ◽  
Maternal Deprivation ◽  
Mild Stress

Behavior and oxidative stress parameters in rats subjected to the animal's models induced by chronic mild stress and 6-hydroxydopamine

2021 ◽  
Vol 406 ◽  
pp. 113226
Author(s):  
Talita Tuon ◽  
Sandra S. Meirelles ◽  
Airam B. de Moura ◽  
Thayse Rosa ◽  
Laura A. Borba ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Oxidative Stress Parameters ◽  
6 Hydroxydopamine ◽  
And Oxidative Stress ◽  
Stress Parameters

Epicatechin treatment generates resilience to chronic mild stress-induced depression in a murine model

2021 ◽  
pp. 113466
Author(s):  
Mirna Guadalupe Martínez-Damas ◽  
Alma Delia Genis-Mendoza ◽  
Verónica Pérez-de la Cruz ◽  
Gabriel Daniel Canela-Tellez ◽  
Ismael Jiménez-Estrada ◽  
...  
Keyword(s):  
Murine Model ◽  
Chronic Mild Stress ◽  
Mild Stress

scholarly journals The Responses of Bioactive Betanin Pigment and Its Derivatives from a Red Beetroot (Beta vulgaris L.) Betalain-Rich Extract to Hypochlorous Acid

2021 ◽  
Vol 22 (3) ◽  
pp. 1155
Author(s):  
Karolina Starzak ◽  
Katarzyna Sutor ◽  
Tomasz Świergosz ◽  
Boris Nemzer ◽  
Zbigniew Pietrzkowski ◽  
...  
Keyword(s):  
Beta Vulgaris ◽  
Hypochlorous Acid ◽  
Innate Immune ◽  
Inflammatory Factors ◽  
Oxygen Species ◽  
Plant Pigments ◽  
Important Food ◽  
Inflammatory Conditions ◽  
Ph Range

Neutrophils produce hypochlorous acid (HOCl) as well as other reactive oxygen species as part of a natural innate immune response in the human body; however, excessive levels of HOCl can ultimately be detrimental to health. Recent reports suggest that betacyanin plant pigments can act as potent scavengers of inflammatory factors and are notably effective against HOCl. Comparison of the in vitro anti-hypochlorite activities of a novel betalain-rich red beetroot (Beta vulgaris L.) extract with its pure betalainic pigments revealed that the extract had the highest anti-hypochlorite activity, far exceeding the activity of all of the betalainic derivatives and selected reference antioxidants. This suggests that it may be an important food-based candidate for management of inflammatory conditions induced by excessive HOCl production. Among all pigments studied, betanidin exhibited the highest activity across the pH range.

scholarly journals Merging the Multi-Target Effects of Kleeb Bua Daeng, a Thai Traditional Herbal Formula in Unpredictable Chronic Mild Stress-Induced Depression

2021 ◽  
Vol 14 (7) ◽  
pp. 659
Author(s):  
Juthamart Maneenet ◽  
Orawan Monthakantirat ◽  
Supawadee Daodee ◽  
Chantana Boonyarat ◽  
Yutthana Chotritthirong ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Chronic Mild Stress ◽  
Antidepressant Activity ◽  
Piper Nigrum ◽  
Psychiatric Disease ◽  
Mild Stress ◽  
Herbal Formula ◽  
Necrosis Factor Alpha ◽  
Unpredictable Chronic Mild Stress

Major depressive disorder (MDD) is a common and debilitating psychiatric disease characterized by persistent low mood, lack of energy, hypoactivity, anhedonia, decreased libido, and impaired cognitive and social functions. However, the multifactorial etiology of MDD remains largely unknown due the complex interaction between genetics and environment involved. Kleeb Bua Daeng (KBD) is a Thai traditional herbal formula that has been used to promote brain health. It consists of a 1:1:1 ratio of the aerial part of Centella asiatica, Piper nigrum fruit, and the petals of Nelumbo nucifera. According to the pharmacological activities of the individual medicinal plants, KBD has good potential as a treatment for MDD. The present study investigated the antidepressant activity of KBD in an unpredictable chronic mild stress (UCMS) mouse model. Daily administration of KBD to UCMS mice ameliorated both anhedonia, by increasing 2% sucrose intake, and hopeless behavior, by reducing immobility times in the forced swimming test (FST) and tail suspension test (TST) without any effect on locomotor activity. The mechanism of KBD activity was multi-modal. KBD promoted neurogenesis by upregulation of brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding (CREB) mRNA expression in the frontal cortex and hippocampus. Daily treatment with KBD significantly reversed UCMS-induced HPA axis dysregulation by upregulating the glucocorticoid receptor (GR) while downregulating serum- and glucocorticoid-inducible kinase 1 (SGK1) and FK506 binding protein 5 (FKBP5) mRNA expression. KBD treatment also normalized proinflammatory cytokine expression including tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1β and IL-6. KBD and its component extracts also exhibited an inhibitory effect in vitro on monoamine oxidase (MAO) A and B. The multiple antidepressant actions of KBD emphasize its potential as an effective, novel treatment for MDD.

scholarly journals Stress Modifies the Expression of Glucocorticoid-Responsive Genes by Acting at Epigenetic Levels in the Rat Prefrontal Cortex: Modulatory Activity of Lurasidone

2021 ◽  
Vol 22 (12) ◽  
pp. 6197
Author(s):  
Paola Brivio ◽  
Giulia Sbrini ◽  
Letizia Tarantini ◽  
Chiara Parravicini ◽  
Piotr Gruca ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chronic Stress ◽  
Chronic Mild Stress ◽  
Male Rats ◽  
Mild Stress ◽  
Experimental Conditions ◽  
Glucocorticoid Responsive Element ◽  
Responsive Element

Epigenetics is one of the mechanisms by which environmental factors can alter brain function and may contribute to central nervous system disorders. Alterations of DNA methylation and miRNA expression can induce long-lasting changes in neurobiological processes. Hence, we investigated the effect of chronic stress, by employing the chronic mild stress (CMS) and the chronic restraint stress protocol, in adult male rats, on the glucocorticoid receptor (GR) function. We focused on DNA methylation specifically in the proximity of the glucocorticoid responsive element (GRE) of the GR responsive genes Gadd45β, Sgk1, and Gilz and on selected miRNA targeting these genes. Moreover, we assessed the role of the antipsychotic lurasidone in modulating these alterations. Chronic stress downregulated Gadd45β and Gilz gene expression and lurasidone normalized the Gadd45β modification. At the epigenetic level, CMS induced hypermethylation of the GRE of Gadd45β gene, an effect prevented by lurasidone treatment. These stress-induced alterations were still present even after a period of rest from stress, indicating the enduring nature of such changes. However, the contribution of miRNA to the alterations in gene expression was moderate in our experimental conditions. Our results demonstrated that chronic stress mainly affects Gadd45β expression and methylation, effects that are prolonged over time, suggesting that stress leads to changes in DNA methylation that last also after the cessation of stress procedure, and that lurasidone is a modifier of such mechanisms.

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