Asperosaponin VI Ameliorates The CMS-Induced Depressive-Like Behaviors By Inducing A Neuroprotective Microglial Phenotype To Restore Hippocampal Synaptic Plasticity Via PPAR-γ Pathway

2021 ◽  
Author(s):  
Xue Jiang ◽  
Saini Yi ◽  
Qin Liu ◽  
Dapeng Su ◽  
Liangyuan Li ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Natural Compound ◽  
Chronic Mild Stress ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Synaptic Function ◽  
Mild Stress ◽  
Real Time Quantitative Pcr ◽  
Ppar Γ ◽  
Microglial Phenotype

Abstract Background: The natural compound asperosaponin VI has shown potential as an antidepressant, but how it works is unclear. Here we explored its effects on mice exposed to chronic mild stress (CMS) and the underlying molecular pathways.Methods: Mice were exposed to CMS for three weeks followed by asperosaponin VI (40 mg/kg) or imipramine (20 mg/kg) for another three weeks. Depression-like behaviors were assessed in the forced swimming test, sucrose preference test, tail suspension test, open field test and novelty-suppressed feeding test. Microglial phenotype and synaptic plasticity were evaluated using immunofluorescence staining, real-time quantitative PCR and enzyme-linked immunosorbent assays in hippocampus of mice. In some experiments, stressed animals were treated with the PPAR-γ antagonist GW9622 to examine its involvement in the effects of asperosaponin VI.Results: Asperosaponin VI ameliorated depression-like behaviors of CMS mice based on all three behavioral tests, and this was associated with a switch of hippocampal microglia from a pro-inflammatory (iNOS+-Iba1+) to neuroprotective (Arg-1+-Iba1+) phenotype. The natural compound also promoted interactions between hippocampal microglia and neurons by enhancing CX3CL1/CX3CR1 and CD200/CD200R, and preserved synaptic plasticity based on PSD95 and CamKIIa levels. These effects of asperosaponin VI were blocked by GW9662. Conclusion: CMS in mice induces a proinflammatory microglial phenotype, disrupting neuron-microglia communication and synaptic function in hippocampus, ultimately leading to depression-like behaviors. Asperosaponin VI may ameliorate the effects of CMS by inducing microglia to adopt a PPAR-γ-dependent neuroprotective phenotype.

Oral supplementation with geranium oil or anise oil ameliorates depressed rat-related symptoms through oils antioxidant effects

2019 ◽  
Vol 17 (2) ◽  
Author(s):  
Karima A. El-Shamy ◽  
Khaled M. M. Koriem ◽  
Nevein N. Fadl ◽  
Marwa H. A. El-Azma ◽  
Mahmoud S. S. Arbid ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Oral Intake ◽  
Chronic Mild Stress ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Psychiatric Disease ◽  
Albino Rats ◽  
Mild Stress ◽  
Immobility Time ◽  
Antioxidant Effects

AbstractBackgroundDepression is a psychiatric disease condition and the chronic mild stress (CMS) model is a well-known and valuable animal model of depression. Geranium oil and anise oil were chosen for such a study. The aim of this research was to establish the geranium oil and anise oil effect to ameliorate CMS-related symptoms.MethodsThis research included 80 male albino rats each group of 10 rats and the animals were divided into two major groups: normal and CMS. The normal group was subdivided into four (control, geranium oil, anise oil and venlafaxine drug) subgroups treated orally with saline, geranium oil, anise oil and venlafaxine drug, respectively, for 4 weeks. The CMS group was subdivided into four (CMS without any treatment, CMS + geranium oil, CMS + anise oil and CMS + venlafaxine drug) subgroups treated orally with geranium oil, anise oil and venlafaxine drug, respectively, for 4 weeks.ResultsThe sucrose consumption in sucrose preference test, the distance traveled test and center square entries test were decreased, while center square duration test, immobility time in tail suspension test and floating time in forced swimming test were increased in CMS. The superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and catalase levels decreased but malondialdehyde and nitric oxide levels increased in brain cerebral cortex and hippocampus areas in CMS. The oral intake of geranium oil and anise oil pushes all these parameters to approach the control levels. These results were supported by histopathological investigations of both brain cerebral cortex and hippocampus tissues.ConclusionsGeranium oil and anise oil ameliorate CMS-related symptoms and this effect were related to the antioxidant effects of oils.

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.

scholarly journals PERUBAHAN PERILAKU GROOMING DAN IMOBILITAS MENCIT BALB/C TERINDUKSI DEPRESI YANG DISUPLEMENTASI TEMPE SEBAGAI SUMBER PARAPROBIOTIK

2020 ◽  
Vol 14 (01) ◽  
pp. 1
Author(s):  
Vanessa Ardianty ◽  
Brian Saputra Manurung
Keyword(s):  
Forced Swim Test ◽  
Chronic Mild Stress ◽  
Tail Suspension Test ◽  
Depression Symptoms ◽  
Depression Symptom ◽  
Mild Stress ◽  
Immobility Time ◽  
Depression Level ◽  
The Common ◽  
Probiotic Food

Depression, a mental disorder marked by sadness, anhedonia and increased fatigability, is becoming more common in this industry 4.0 era. Nowadays, depression affects approximately 322 million people around the world (more than 14 million in Indonesia) and gives major contribution to the rise of global burden of disease. Although antidepressant is considered the common treatment for depression, recent studies show a possibility to treat depression by altering gut microbiome of the patient, by giving them probiotic food. Tempeh is a globally well-known Indonesian paraprobiotic food which already proven to modulate gut microbiota. This research aimed to find out the effect of tempeh to depression symptom as expressed in Balb/c mice behaviors. The methods used was to feed tempeh or tempeh starter to mice which were depressed-induced by Unpredictable Chronic Mild Stress (UCMS) procedure. Parameter measured were depression level of the Balb/c mice based on immobility times and grooming durations acquired from tail suspension test, forced swim test, sucrose splash test and coat state score. The result showed that tempeh supplementation did not affect coat states and grooming durations but tend to improve immobility times of the Balb/c mice. Meanwhile, tempeh starter supplementation tends to improve the immobility time and kept coat state clean/tidy, but lowered grooming duration. In conclusion, supplementation of paraprobiotic tempeh, especially in starter form, tend to improve depression symptoms. Keywords: depression, mice, paraprobiotic, tempeh

Effect of (4a) a novel 5-HT3 receptor antagonist on chronic unpredictable mild stress induced depressive-like behavior in mice: an approach using behavioral tests battery

2015 ◽  
Vol 26 (1) ◽  
Author(s):  
Yeshwant Kurhe ◽  
Radhakrishnan Mahesh ◽  
Deepali Gupta ◽  
Devadoss Thangaraj
Keyword(s):  
Lipid Peroxidation ◽  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Brain Homogenate ◽  
Therapeutic Interventions ◽  
Mild Stress ◽  
Behavioral Alterations ◽  
Biochemical Alterations ◽  
Immobility Time

AbstractThe inconsistent therapeutic outcome necessitates designing and identifying novel therapeutic interventions for depression. Hence, the present study deals with the investigation of antidepressant-like effects of a novel 5-HTAnimals were subjected to different stressors for a period of 28 days. On day 15 after the subsequent stress procedure, mice were administered with (4a) (2 and 4 mg/kg p.o.), escitalopram (10 mg/kg p.o.), or vehicle (10 mL/kg p.o.) until day 28 along with the CUMS. Thereafter, behavioral battery tests like locomotor score, sucrose preference test, forced swim test (FST), tail suspension test (TST), and elevated plus maze (EPM) were performed. Biochemical assays like lipid peroxidation, nitrite levels, reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) were estimated in the mice brain homogenate.(4a) Dose dependently attenuated the behavioral alterations by increasing the sucrose consumption, reducing the immobility time in FST and TST, increasing the open arm number of entries and time in EPM. Furthermore, biochemical alterations were reversed by (4a) as examined by reduced lipid peroxidation and nitrite levels and elevated antioxidant enzyme levels like GSH, catalase and SOD.(4a) exhibits antidepressant potential by reversing the CUMS induced behavioral and biochemical changes in mice.

scholarly journals ANTIDEPRESSANT-LIKE ACTIVITY OF TRANS-ANETHOLE IN UNSTRESSED MICE AND STRESSED MICE

2019 ◽  
pp. 121-127
Author(s):  
DINESH DHINGRA ◽  
SUDHA
Keyword(s):  
Preference Test ◽  
Tail Suspension Test ◽  
Plasma Corticosterone ◽  
Monoamine Oxidase A ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Male Mice ◽  
Mao A ◽  
Sucrose Preference Test ◽  
Plasma Nitrite

Objectives: The present study was undertaken to investigate the antidepressant potential of trans-anethole in unstressed and stressed male mice. Methods: Swiss albino male mice were exposed to chronic unpredictable mild stress for 21 successive days. Simultaneously, trans-anethole (12.5 mg/kg, 25 mg/kg, and 50 mg/kg) and fluoxetine (20 mg/kg) per se were administered for 21 successive days to separate groups of unstressed and stressed mice. The effect of drugs on depressive-like behavior of mice was tested by tail suspension test (TST) and sucrose preference test. Results: Trans-anethole (25 mg/kg) and fluoxetine significantly decreased the immobility period of unstressed and stressed mice in TST as compared to their respective control. These drugs significantly restored the reduced sucrose preference (%) in stressed mice. Trans-anethole did not show any significant effect on locomotor activity of mice. Antidepressant-like activity of trans-anethole (25 mg/kg) was found to be comparable to fluoxetine. Trans-anethole and fluoxetine significantly inhibited brain monoamine oxidase-A (MAO-A) activity, decreased plasma nitrite, brain malondialdehyde, and increased brain reduced glutathione levels and catalase activity in unstressed and stressed mice. The drugs significantly reversed stress-induced increase in plasma corticosterone levels. Conclusion: Trans-anethole produced significant antidepressant-like activity in unstressed and stressed mice, possibly through inhibition of brain MAO-A activity and alleviation of oxidative stress. Reversal of stress-induced increase in plasma corticosterone levels might also be responsible for antidepressant-like activity of trans-anethole in stressed mice.

scholarly journals ANTIDEPRESSANT-LIKE ACTIVITY OF FLOWERS OF TECOMELLA UNDULATA IN MICE SUBJECTED TO CHRONIC UNPREDICTABLE MILD STRESS

2019 ◽  
Vol 12 (1) ◽  
pp. 130
Author(s):  
Dinesh Dhingra ◽  
Deepak Deepak
Keyword(s):  
Young Male ◽  
Ethanol Extract ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Plasma Corticosterone ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Tecomella Undulata ◽  
Plasma Nitrite

Objective: Flowers of Tecomella undulata have been reported to be a rich source of flavonoids such as rutin and quercetin. The present study was designed to evaluate the effect of ethanol extract of flowers of T. undulata on chronic unpredictable mild stress (CUMS)-induced depression in Swiss young male albino mice.Methods: The mice were subjected to CUMS for 21 successive days. Ethanol extract of the flowers (50, 100, and 200 mg/kg, p.o.) and fluoxetine (20 mg/kg, p.o.) per se was administered for 21 successive days to separate groups of unstressed and stressed mice. Tail suspension test (TST) and sucrose preference test were used to evaluate the effect of the extract on depression-like behavior in mice.Results: Extract of flowers of T. undulata (100 and 200 mg/kg) significantly decreased immobility period of stressed mice in TST, indicating significant antidepressant-like activity of the extract. Stress-induced reduced sucrose preference was significantly restored by the extract. There was no significant effect on locomotor activity of mice by the extract and fluoxetine. The extract significantly reversed stress-induced increase in brain malondialdehyde levels; plasma nitrite and corticosterone levels; and also significantly reversed the stress-induced decrease in reduced glutathione and catalase levels. There was no significant effect of the extract on brain MAO-A activity in both unstressed and stressed mice.Conclusion: These results indicated that ethanol extract of flowers of T. undulata showed significant antidepressant-like activity in mice subjected to CUMS, probably through alleviation of oxidative stress and decrease in plasma corticosterone levels.

scholarly journals Electroacupuncture Reverses CUMS-Induced Depression-Like Behaviors and LTP Impairment in Hippocampus by Downregulating NR2B and CaMK II Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Shuo Jiang ◽  
Zui Shen ◽  
Wenlin Xu
Keyword(s):  
Synaptic Plasticity ◽  
Global Mental Health ◽  
Hippocampal Slices ◽  
Preference Test ◽  
Long Term Potentiation ◽  
Antidepressant Effect ◽  
Feeding Time ◽  
Mild Stress ◽  
Protein Levels ◽  
Behavior Of Rats

Objective. Depression is a global mental health problem with high disability rate, which brings a huge disease burden to the world. Electroacupuncture (EA) has been shown to be an effective method for the treatment of depression. However, the mechanism underling the antidepressant effect of EA has not been clearly clarified. The change of synaptic plasticity is the focus in the study of antidepressant mechanism. This study will observe the effect of EA on LTP of hippocampal synaptic plasticity and explore its possible mechanism. Methods. The depression-like behavior rat model was established by chronic unpredictable mild stress (CUMS). EA stimulation (Hegu and Taichong) was used to treat the depressed rats. The depression-like behavior of rats was tested by weight measurement, open field test, depression preference test, and novelty suppressed feeding test. Long-term potentiation (LTP) was recorded at CA1 synapses in hippocampal slices by electrophysiological method. N-methyl-D-aspartate receptor subunit 2B (NR2B) and calmodulin-dependent protein kinase II (CaMK II) protein levels were examined by using western blot. Results. After the establishment of CUMS-induced depression model, the weight gain rate, sucrose preference rate, line crossing number, and rearing times of rats decreased, and feeding time increased. At the same time, the LTP in hippocampus was impaired, and the expressions of NR2B and CaMK II were upregulated. After EA treatment, the depression-like behavior of rats was improved, the impairment of LTP was reversed, and the expression levels of NR2B and CaMK II protein were downregulated. Conclusion. EA can ameliorate depression-like behaviors by restoring LTP induction, downregulating NR2B and CaMK II expression in CUMS model rats, which might be part of the mechanism of EA antidepressant.

scholarly journals A Comparison of Isolation Stress and Unpredictable Chronic Mild Stress for the Establishment of Mouse Models of Depressive Disorder

2021 ◽  
Vol 14 ◽  
Author(s):  
Jin-Seok Lee ◽  
Ji-Yun Kang ◽  
Chang-Gue Son
Keyword(s):  
Animal Models ◽  
Depressive Disorder ◽  
Depressive Disorders ◽  
Chronic Mild Stress ◽  
Tail Suspension Test ◽  
Modern Society ◽  
Mild Stress ◽  
Isolation Stress ◽  
Unpredictable Chronic Mild Stress ◽  
Serum Corticosterone

This study aimed to help to understand the influence of stress on depression, which reflects the social environments of especially solitary life and the increasing prevalence of depressive disorders. To determine the distinguishable features of two-representative animal models of stress-induced depressive disorder, we compared isolation stress (IS) and unpredictable chronic mild stress (UCMS). After 4-week of stress, both models showed significant depressive- and anxiety-like behaviors in an open field test (OFT; p &lt; 0.01 for IS, p &lt; 0.01 for UCMS), forced swimming test (FST; p &lt; 0.01 for IS, p &lt; 0.01 for UCMS), and tail suspension test (TST; p &lt; 0.01 for IS, p &lt; 0.05 for UCMS) along with alterations in serum corticosterone levels, serotonin activity in the dorsal raphe nuclei (DRN) and microglial activity in the dentate gyrus of the hippocampus (p &lt; 0.05 for both parameters). In a comparison of the two stress models, IS strongly induced depressive and anxiety features, as indicated by all parameters: behavior test scores (p &lt; 0.05 for OFT, FST, and TST), serum corticosterone levels (p &lt; 0.05), immunohistological alterations for serotonin activity (p &lt; 0.05) and microglial activity (p = 0.072). Our results indicate the suitability of IS for the development of animal models of depressive disorders and may reveal the medical impact of social isolation environment in modern society.

scholarly journals Putative Role of Monoaminergic Systems in Antidepressant and Anxiolytic Effects of Naringin in Mice: An Interaction Study with Receptor Antagonists

2021 ◽  
pp. 661-676
Author(s):  
G. E. Anyanwu ◽  
V. O. Atuadu ◽  
B. Ben-Azu ◽  
E. A. Esom ◽  
J. N. Nto ◽  
...  
Keyword(s):  
Anxiolytic Effect ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Receptor Interaction ◽  
Control Group ◽  
Mild Stress ◽  
Receptor Antagonists ◽  
Neurotransmitter Receptor ◽  
Immobility Time

Aim: Stress-related disorders like depression and anxiety represent one of the greatest therapeutic challenges globally. Although previous studies have revealed the antidepressant-like potentials of naringin, the neurotransmitter receptor interaction mechanisms of action have not been studied, hence, this study was carried out to evaluate the role of neurotransmitter-receptor antagonists in the antidepressant-like effects of naringin in mice. Method: Male Swiss mice were subjected to chronic unpredictable mild stress (CUMS) apart from mice in the control group. The mice were then pretreated with different neurotransmitter antagonists; metergoline (4 mg /kg i.p.), a 5-HT1 - and 5-HT2 -receptor antagonist; propranolol; (0.2 mg/kg i.p.), β1,2-noradrenoceptor antagonist or haloperidol (0.2 mg/kg i.p.), D 2 -dopaminergic receptor antagonists prior to the administration of naringin or vehicle (10 mL/kg). The antidepressant-like and anxiolytic effects of naringin were evaluated 30 min later using the tail suspension test (TST), open-field test (OFT), sucrose preference test (SPT) and elevated plus maze (EPM) tests paradigms. Results: Administration of naringin following CUMS significantly decrease immobility time and locomotion activity in TST and OFT respectively, relative to control while increasing preference to sucrose in SPT, open arm entries as well as time spent in open arm in EPM, relative to control suggesting antidepressant-like property. Pretreatment with metergoline, propranolol, and haloperidol following CUMS increased immobility time in TST, locomotor activity in OFT and IOAA in the EPM. Reduced preference for sucrose in SPT, open arm entry and duration in EPM relative to control (p < 0.05), however, these effects were attenuated by naringin. Conclusion: These findings suggest that the antidepressant-like activity exhibited by naringin might be mediated via interactions with 5-HTergic, noradrenergic, and dopaminergic receptors, while the anxiolytic effect might involve interaction with both 5-HTergic and noradrenergic receptors.

scholarly journals Jianpi Jieyu Decoction, An Empirical Herbal Formula, Exerts Psychotropic Effects in Association With Modulation of Gut Microbial Diversity and GABA Activity

2021 ◽  
Vol 12 ◽  
Author(s):  
Lanying Liu ◽  
Zhilu Zou ◽  
Jiangwei Yang ◽  
Xiaoqi Li ◽  
Boran Zhu ◽  
...  
Keyword(s):  
Serum Level ◽  
Gut Microbiota ◽  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Gamma Aminobutyric Acid ◽  
Object Recognition Test ◽  
Microbial Distribution

Background: Recent studies suggest that gut microbiota was associated with the bidirectional gut-brain axis which could modulate neuropsychological functions of the central nervous system. Gut microbiota could produce gamma aminobutyric acid (GABA) that could modulate the gut–brain axis response. Jianpi Jieyu (JPJY) decoction, a traditional Chinese formula, is mainly composed of Astragalus membranaxeus and Radix Pseudostellariae. Although the JPJY decoction has been used to treat the depression in China, the potential action of its antidepressant has not been well understood. Thus this study was aim to investigate the role of JPJY improve gut microbiota homeostasis in the chronic stress induced depressive mice.Methods: The antidepressant effect of JPJY on chronic unpredictable mild stress (CUMS) mice was evaluated by using sucrose preference test, tail suspension test and forced swim test. Fatigue-like behaviors were evaluated using degree of redness, grip strength test, and exhaustive swimming test. The new object recognition test was used to evaluate cognition performance. Fecal samples were collected and taxonomical analysis of intestinal microbial distribution was conducted with 16S rDNA. Serum level of GABA was measured using high performance liquid chromatography (HPLC). The expression of GluR1 and p-Tau protein in the hippocampus was determined using Western blotting.Results: The dose of 9.2 g/kg JPJY produced antidepressant-like effects. JPJY and its major components also modulated gut microbiota diversity in the CUMS mice. Serum level of GABA and the expressions of hippocampal GluR1 and p-Tau were reversed after the administration of JPJY in CUMS mice.Conclusion: JPJY regulates gut microbiota to produce antidepressant-like effect and improve cognition deficit in depressive mice while its molecular mechanism possibly be enhanced NR1 and Tau expression in hippocampus and increased GABA in serum.

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