scholarly journals Musk (Moschus moschiferus) Attenuates Changes in Main Olfactory Bulb of Depressed Mice: Behavioral, Biochemical, and Histopathological Evidence

2021 ◽  
Vol 15 ◽  
Author(s):  
Hailah M. Almohaimeed ◽  
Ashwaq H. Batawi ◽  
Zuhair M. Mohammedsaleh ◽  
Soad Al Jaouni ◽  
Samiah A. Mutlq Alsawat ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Chronic Stress ◽  
Inflammatory Cytokines ◽  
Histopathological Examination ◽  
Corticosterone Level ◽  
Mild Stress ◽  
Main Olfactory Bulb ◽  
Immobility Time ◽  
Anti Inflammatory ◽  
Moschus Moschiferus

BackgroundMusk (Moschus moschiferus) has been described to have a significant impact on the central nervous system, as well as anticonvulsion and antidepressant effects. This study was designed to evaluate the efficacy of musk in alleviating alterations induced in olfactory bulb of depressed mice exposed to chronic stress and identify the mechanism behind it.MethodsFifty male albino mice were divided into five groups (n = 10 each): control, musk, chronic unpredictable mild stress (CUMS), fluoxetine-treated, and musk-treated groups were included in this study. Behavioral changes and serum levels of corticosterone and proinflammatory cytokines included tumor necrosis factor α, interleukin 6, and oxidant/antioxidant profile were assessed at the end of the experiment. Main olfactory bulb (MOB) has been processed for histopathological examination. Gene expression of caspase-3, glial fibrillary acidic protein, and Ki67 were assessed in the MOB using quantitative real-time polymerase chain reaction.ResultsThe study showed that musk inhalation significantly reduced (p < 0.001) corticosterone level, immobility time, inflammatory cytokines, and oxidative stress markers in CUMS-exposed mice compared to the untreated CUMS group. Musk lessened CUMS-associated neuronal alterations in the MOB and significantly reduced apoptosis and enhanced neural cell proliferation (p < 0.001) comparable to fluoxetine. Musk significantly enhanced the level of antioxidants in the serum and significantly reduced inflammatory cytokines. The anti-inflammatory and antioxidant activity of musk and its constituents seemed to be behind its neuroprotective effect observed in this study.ConclusionMusk effectively ameliorated the chronic stress–induced behavioral, biochemical, and neuronal structural changes in MOB mostly through its antioxidant and anti-inflammatory effect.

scholarly journals An Ethanolic Extract of Cucurbita pepo L. Seeds Modifies Neuroendocrine Disruption in Chronic Stressed Rats and Adrenal Expression of Inflammatory Markers and HSP70

2021 ◽  
Vol 12 ◽  
Author(s):  
Hailah M. Almohaimeed ◽  
Shereen Hamed ◽  
Hanan S. Seleem ◽  
Ashwaq H. Batawi ◽  
Zuhair M. Mohammedsaleh ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Cucurbita Pepo ◽  
Structural Changes ◽  
Adrenal Glands ◽  
Corticosterone Level ◽  
Ethanolic Extract ◽  
Albino Rats ◽  
Mild Stress ◽  
Immobility Time ◽  
Anti Inflammatory

Background: Pumpkins (Cucurbita pepo L.) were described to have antioxidant, anti-inflammatory, anti-fatigue, and antidepressant-like effect. The adrenal gland is an important stress-responsive organ that maintains homeostasis during stress.Objectives: This study aimed to assess the efficacy of the administration of Cucurbita pepo L. (CP) extract in relieving behavioral, biochemical, and structural changes in the adrenal gland induced by exposure to chronic unpredictable mild stress (CUMS) and to explore the mechanism behind this impact.Materials and Methods: Forty male albino rats were divided into 4 groups (n = 10): control, CUMS, fluoxetine-treated, and CP-treated groups. Behavioral changes, corticosterone level, pro-inflammatory cytokines TNF-α and IL-6, and oxidant/antioxidant profile were assessed in the serum at the end of the experiment. Adrenal glands were processed for histopathological and immunohistochemical assessment. Gene expression of caspase-3 and Ki67 and heat shock protein 70 (HSP70) were assessed in adrenal glands using RT-PCR.Results: The CP extract significantly reduced the corticosterone level (p < 0.001), immobility time (p < 0.001), and inflammatory and oxidative changes associated with CUMS-induced depression compared to the untreated group. The CP extract alleviated CUMS-induced adrenal histopathological changes and significantly reduced apoptosis (p < 0.001) and significantly upregulated antioxidant levels in the serum.Conclusion:Cucurbita pepo L. effectively ameliorated the chronic stress-induced behavioral, biochemical, and adrenal structural changes mostly through its antioxidant and anti-inflammatory effects.

scholarly journals Antidepressant-Like Effect and Mechanism of Action of Honokiol on the Mouse Lipopolysaccharide (LPS) Depression Model

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2035 ◽  
Author(s):  
Bo Zhang ◽  
Ping-Ping Wang ◽  
Kai-Li Hu ◽  
Li-Na Li ◽  
Xue Yu ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Mechanism Of Action ◽  
Tail Suspension Test ◽  
Interferon Γ ◽  
Biologically Active ◽  
Free Calcium ◽  
Immobility Time ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Pro Inflammatory Cytokines

There is growing evidence that neuroinflammation is closely linked to depression. Honokiol, a biologically active substance extracted from Magnolia officinalis, which is widely used in traditional Chinese medicine, has been shown to exert significant anti-inflammatory effects and improve depression-like behavior caused by inflammation. However, the specific mechanism of action of this activity is still unclear. In this study, the lipopolysaccharide (LPS) mouse model was used to study the effect of honokiol on depression-like behavior induced by LPS in mice and its potential mechanism. A single administration of LPS (1 mg/kg, intraperitoneal injection) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), without affecting autonomous activity. Pretreatment with honokiol (10 mg/kg, oral administration) for 11 consecutive days significantly improved the immobility time of depressed mice in the FST and TST experiments. Moreover, honokiol ameliorated LPS-induced NF-κB activation in the hippocampus and significantly reduced the levels of the pro-inflammatory cytokines; tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). In addition, honokiol inhibited LPS-induced indoleamine 2,3-dioxygenase (IDO) activation and quinolinic acid (a toxic product) increase and reduced the level of free calcium in brain tissue, thereby inhibiting calcium overload. In summary, our results indicate that the anti-depressant-like effects of honokiol are mediated by its anti-inflammatory effects. Honokiol may inhibit the LPS-induced neuroinflammatory response through the NF-κB signaling pathway, reducing the levels of related pro-inflammatory cytokines, and furthermore, this may affect tryptophan metabolism and increase neuroprotective metabolites.

Effects of Chrysin on Serum Corticosterone Levels and Brain Oxidative Damages Induced by Immobilization in Rat

2020 ◽  
Vol 20 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Tahereh Farkhondeh ◽  
Sediqeh Jalali ◽  
Milad Ashrafizadeh ◽  
Saeed Samarghandian ◽  
Fariborz Samini
Keyword(s):  
Chronic Stress ◽  
Restraint Stress ◽  
Neuroprotective Effect ◽  
Group Versus ◽  
Corticosterone Level ◽  
Serum Corticosterone ◽  
Oxidative Damages ◽  
Stressed Group ◽  
Immobility Time ◽  
The Impact

Background: Chrysin (CH) is one of the main flavonoids of vegetables, fruits, and plants, the neuroprotective effect of which has been demonstrated in this study. Objective: The aim of the current investigation is the evaluation of the impact of chrysin (CH) on serum corticosterone level. Additionally, depression due to chronic stress was studied in animal models. Methods: The rats were restrained for 1 hour daily for 3 weeks. During these weeks, all animals were daily injected with either vehicle or CH (10, 20, 30 µg/kg). Results: Present data indicated that the serum corticosterone levels markedly elevated in the stressed group versus the non-stressed group (p<0.001). The serum corticosterone levels were significantly lower in the stress-exposed rats administered with CH versus the stress-exposed non- CH-treated rats (p<0.05). In addition, immobility time significantly increased in the rats submitted to restraint stress versus the non-stressed group (p<0.001). Also, the number of crossing significantly decreased in the rats submitted to restraint stress versus non-stressed rats (p<0.001). The immobility time and the number of crossing were also reduced in the CH-administrated stressed rats (30 mg/kg) versus non-treated stressed group (p<0.001, p<0.05, respectively). CH also ameliorated the MDA and GSH content as well as antioxidant enzymes activities in stressed rats (p<0.05). Conclusion: The present study suggested that CH might be useful for the management of depressant-like effects induced by chronic stress via decreasing oxidative damage in the brain.

scholarly journals Brain-Derived Neurotropic Factor (BDNF) Mediates the Protective Effect of L.Cucurbita Pepo on Salivary Glands of Depressed Rat Evident by Structural, Biochemical and Molecular Study

2021 ◽  
Author(s):  
Hailah M. ALmohaimeed ◽  
Emad A. Albadawi ◽  
Zuhair M. Mohammedsaleh ◽  
Hadel M. Alghabban ◽  
Hanan S. Seleem ◽  
...  
Keyword(s):  
Salivary Glands ◽  
Inflammatory Cytokines ◽  
Serum Levels ◽  
Albino Rats ◽  
Mild Stress ◽  
Ductal Cells ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
The Impact ◽  
Pro Inflammatory Cytokines

Abstract BackgroundAcute and chronic stresses affect the salivary glands which are the source of plasma BDNF during stressful conditions. Pumpkin is a medicinal plant with an evident antioxidant, anti-inflammatory and potential antidepressant effects. This work was conducted to assess the impact of chronic unpredictable mild stress (CUMS) on the structure of albino rats’ salivary glands and evaluate the role of pumpkin extract (Pump) in ameliorating this effect. MethodsFour groups (n=10 each) of male albino rats included in this study; the control, CUMS, CUMS+fluoxetine and (CUMS+Pump). Corticosterone, pro-inflammatory cytokines (TNF-α & IL-6) and the oxidant/antioxidant profile were all assessed in the serum. BDNF mRNA level was measured in the salivary glands using qRT-PCR. Histopathological changes of the salivary glands were also assessed. ResultsDepression was confirmed behaviorally and biochemically. Exposure to CUMS significantly (p< 0.001) up-regulated the level of serum corticosterone. CUMS induced degenerative changes in the secretory and ductal system, atrophy of acini and increased apoptosis of the acinar and ductal cells. Both fluoxetine and Pump significantly up-regulated (p<0.001) BDNF expression in the salivary glands and ameliorated the CUMS-induced histopathological alterations in the salivary glands. Pumpkin significantly (p<0.001) increased the serum levels of antioxidant enzymes SOD, GPX and CAT and reduced the serum levels of the pro-inflammatory cytokines TNF-α, IL-6.ConclusionPumpkin ameliorates chronic stress-induced depression in rats by exerting a promising anti-inflammatory, antioxidant and anti-depressant-like effects in rats exposed to CUMS. Pump subsequently improved stress-induced structural changes in the salivary glands that might be due to the glands up-regulation of BDNF expression.Trial registrationNot applicable.

scholarly journals Antidepressant-Like Effect of Geniposide in Mice Exposed to a Chronic Mild Stress Involves the microRNA-298-5p-Mediated Nox1

2021 ◽  
Vol 13 ◽  
Author(s):  
Tianyu Zou ◽  
Jielin Zhang ◽  
Yongxiu Liu ◽  
Yiming Zhang ◽  
Kazuo Sugimoto ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Common Mental Disorder ◽  
Tail Suspension Test ◽  
Luciferase Reporter ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Luciferase Reporter Gene ◽  
Neuroprotective Effects ◽  
Immobility Time ◽  
Gene Assay

Depression is a common mental disorder that presents a considerable challenge for public health. The natural product geniposide has neuroprotective effects on depression, but the underlying mechanism behind these effects had remained undefined. The present study was designed to investigate the role of microRNAs (miRs) in this mechanism. It studied mice with depression-like behavior established by exposure to chronic unpredictable mild stress (CUMS) for 2 months. The CUMS mice were intragastrically fed with geniposide at a dose of 10 ml/kg daily for two consecutive weeks. We monitored the depression-like behaviors of the CUMS mice by the forced swimming test (FST) and tail suspension test (TST). Then, we measured the cerebral expression of miR-298-5p and NADPH oxidase 1 (Nox1) mRNA in the CUMS mice by the RT-qPCR. The targeting relationship between miR-298-5p and Nox1 was evaluated by dual-luciferase reporter gene assay. The concentrations of adenosine triphosphate (ATP) and reactive oxygen species (ROS) were determined by the CellTiter-Glo® and flow cytometry, respectively. The mitochondrial membrane potential (MMP) was detected using JC-1 staining. Moreover, the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and TGF-β) was determined by ELISA, RT-qPCR, and western blot analysis. We found that miR-298-5p was poorly-expressed while Nox1 was highly-expressed in the brain tissues of the CUMS-induced mice. Intriguingly, Geniposide treatment reversed the behavioral abnormalities of CUMS mice, including shortened immobility time. Geniposide inhibited the Nox1 expression by increasing miR-298-5p levels. There were increased ATP content and MMP and reduced contents of ROS and inflammatory cytokines in the CUMS mice receiving geniposide treatment. Hence, this study revealed an antidepressant effect of geniposide on CUMS-induced depression-like behavior in mice by down-regulating the miR-298-5p-targeted Nox1. This highlights a novel candidate target for the treatment of depression.

Pro- and anti-inflammatory cytokines expression in rat's brain and spleen exposed to chronic mild stress: Involvement in depression

2011 ◽  
Vol 225 (1) ◽  
pp. 135-141 ◽  
Author(s):  
Zili You ◽  
Chunmei Luo ◽  
Wenzheng Zhang ◽  
Yubo Chen ◽  
Jiajia He ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Anti Inflammatory

scholarly journals ANTIDEPRESSANT-LIKE EFFECT OF DIMETHYL FUMARATE AND ASTROCYTE CHANGES IN HIPPOCAMPUS OF MICE SUBMMITED TO MODEL OF DEPRESSION

2021 ◽  
pp. 8
Author(s):  
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Protein Expression ◽  
Chronic Stress ◽  
Forced Swim Test ◽  
Dimethyl Fumarate ◽  
Acidic Protein ◽  
Mild Stress ◽  
Immobility Time ◽  
High Prevalence ◽  
Group 3

Introduction: Depression is a psychiatric condition of high prevalence worldwide and is associated with inflammation. Dimethyl fumarate, used to treat psoriasis and multiple sclerosis, has demonstrated an anti-inflammatory effect. Objective: To evaluate the effect of dimethyl fumarate on depression, through the immobility time in the forced swim test, and on astrocyte proliferation, through the expression of glial fibrillary acidic protein in the hippocampus of mice submitted to Chronic Unpredictable Mild Stress- induced model of depression. Methods: Male mice were divided into three groups: control(1), stressed(2), stressed+dimethyl fumarate (3). Groups 2 and 3 were subjected to 28 days of exposure to unpredictably applied stressors. From the 14th day, group 3 was treated with dimethyl fumarate (oral). At the end, the hippocampus was removed to determination of glial fibrillary acidic protein expression by immunofluorescence. Results: The immobility time was increased by chronic stress compared to the control and the treatment with dimethyl fumarate decreased this parameter, compared to the stressed group [F (9, 92) = 6,460; 1vs2: p <0.01, 2vs3: p <0.001]. Glial fibrillary acidic protein expression was reduced by chronic stress compared to control in the two areas of the hippocampus analyzed and treatment with dimethyl fumarate did not interfere in this parameter [CA1: F (2, 6) = 5.173, 1vs2: p <0.05; Dentate gyrus: F (2, 7) = 31.44, 1vs2: p <0.001]. Conclusion: Dimethyl fumarate has antidepressant-like effect in mice, however more studies need to be carried out to elucidate the neuroinflammatory mechanism of this drug.

scholarly journals Effects of the Ethanol Extract of Dipterocarpus alatus Leaf on the Unpredictable Chronic Mild Stress-Induced Depression in ICR Mice and Its Possible Mechanism of Action

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3396 ◽  
Author(s):  
Daodee ◽  
Monthakantirat ◽  
Ruengwinitwong ◽  
Gatenakorn ◽  
Maneenet ◽  
...  
Keyword(s):  
Corticosterone Level ◽  
Ethanol Extract ◽  
Chronic Mild Stress ◽  
Tail Suspension Test ◽  
Selective Inhibition ◽  
Mild Stress ◽  
Unpredictable Chronic Mild Stress ◽  
Immobility Time ◽  
Dipterocarpus Alatus

Treatment of the unpredictable chronic mild stress (UCMS) mice with the ethanol extract of Dipterocarpus alatus leaf attenuated anhedonia (increased sucrose preference) and behavioral despair (decreased immobility time in tail suspension test (TST) and forced swimming test (FST)). The extract not only decreased the elevation of serum corticosterone level and the index of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis, caused by UCMS, but also ameliorated UCMS-induced up-regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) mRNA expression and down-regulation of cyclic AMP-responsive element binding (CREB) and brain-derived neurotrophic factor (BDNF) mRNAs in frontal cortex and hippocampus. In vitro monoamine oxidase (MAO) inhibition assays showed that the extract exhibited the partial selective inhibition on MAO-A. HPLC analysis of the extract showed the presence of flavonoids (luteolin-7-O-glucoside, kaempferol-3-glucoside, rutin) and phenolic acids (gallic acid, ferulic acid, and caffeic acid) as major constituents.

Comparative Proteomics of Rat Olfactory Bulb Reveal Insights Into Susceptibility and Resilience to Chronic-Stress-Induced Depression or Anxiety

2021 ◽  
Author(s):  
Dan Liu ◽  
Xiao Cai ◽  
Lixiang Wang ◽  
Faping Yi ◽  
Wei Liao ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Chronic Stress ◽  
Proteome Analysis ◽  
Chronic Mild Stress ◽  
Maladaptive Behavior ◽  
Regulation System ◽  
Mild Stress ◽  
Potential Candidate ◽  
Bioinformatics Analyses ◽  
Protein Targets

Abstract As a main risk factor of both anxiety and depression, chronic stress can cause the abnormality of olfactory bulb (OB). However, the unique and common neurobiological underpinnings underlying the OB dysfunction of these two disorders are still poorly understood. Previously, we have built depression-susceptible (Dep-Sus), anxiety-susceptible (Anx-Sus) and insusceptible (Insus) groups through the use of a valid chronic mild stress (CMS) regime. To continuously explore the protein expression changes in these three groups, comparative quantitative proteomics analysis was conducted on the rat OB as crucial part of the olfactory system. Next, bioinformatics analyses were implemented whereas protein expressions were independently analyzed by parallel reaction monitoring (PRM) or Western blot (WB). The OB-proteome analysis identified totally 133 differentially expressed proteins as a CMS response. These deregulated proteins were involved in multiple functions and significant pathways potentially correlated with phenotypes of maladaptive behavior of depression or anxiety as well as adaptive behavior, and hence might act as potential candidate protein targets. The subsequent PRM-based or WB-based analyses showed that changes in Nefl, Mtmr7 and Tk2; Prkaca, Coa3, Cox6c2, Lamc1 and Tubal3; and Pabpn1, Nme3, Sos1 and Lum were uniquely associated with Dep-Sus, Anx-Sus, and Insus groups, respectively. This suggested that the identical CMS differently impacted the olfactory protein regulation system. To sum up, our present data as a useful proteomics underpinning provided the common and distinct molecular insights into the biochemical understanding of OB dysfunction underlying susceptibility and resiliency to chronic-stress-induced anxiety or depression.

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