scholarly journals Botanical Drug Puerarin Ameliorates Liposaccharide-Induced Depressive Behaviors in Mice via Inhibiting RagA/mTOR/p70S6K Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Jia Zhao ◽  
Yizhen Jia ◽  
Wei Zhao ◽  
Huixin Chen ◽  
Xiuying Zhang ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Forced Swim Test ◽  
Protein A ◽  
Antidepressant Drugs ◽  
Tail Suspension Test ◽  
Quantitative Real Time Pcr ◽  
Close Proximity ◽  
Sequencing Technique ◽  
Botanical Drug ◽  
The Brain

Background. The depressive symptom hallmarks the progression of the neurodegenerative diseases, especially Alzheimer’s disease. Bacterial infection is related to inflammation and depression. The present project thereby examined whether botanical drug puerarin could attenuate liposaccharide- (LPS-) induced depressive behaviors in mice. Methods. Adult male C57BL/6N mice were sequentially treated with LPS and puerarin and evaluated for the depressive behaviors by tail suspension test and forced swim test. The brain tissues were profiled for the molecular targets of puerarin by next-generation RNA sequencing technique. Candidate targets were further verified in LPS-treated mice, neural stem cells, and highly differentiated PC12 cell line. Results. Puerarin ameliorated LPS-induced depression in the mice. RNA sequencing profiles revealed that puerarin altered the expression of 16 genes while markedly downregulated Ras-related GTP-binding protein A (RagA) in LPS-treated mice. The effect of puerarin on RagA expression was confirmed by immunostaining, Western blot, and quantitative real-time PCR (qRT-PCR). Biochemical studies showed that puerarin inhibited RagA/mTOR/p70S6K pathway, attenuated the accumulation of mTORC1 in close proximity to lysosome, and reduced the production of proinflammatory cytokines. Conclusions. Botanical drug puerarin attenuated inflammation and depressive behaviors in LPS-challenged mice by inhibiting RagA/mTOR/p70S6K pathways. Puerarin may be a lead compound for the new antidepressant drugs.

scholarly journals Anti-Depressant Activity of the Leaves of Zanthoxylum Armatum on Swiss Albino Mice

2020 ◽  
Vol 8 (02) ◽  
pp. 46-50
Author(s):  
Chandrajeet Kumar Yadav ◽  
Kamal Poudel ◽  
Roshan Mehta ◽  
Amit Kumar Shrivastava
Keyword(s):  
Methanolic Extract ◽  
Forced Swim Test ◽  
Antidepressant Drugs ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Medical Problem ◽  
Mild Stress ◽  
Swiss Albino Mice ◽  
Zanthoxylum Armatum ◽  
Albino Mice

INTRODUCTION Depression is a global mental disorder that has high incidence, high recurrence, and high self-mutilation and suicide rates. Although the antidepressant drugs are available for the treatment, depression still continues to be a major medical problem. The present study was designed to study the anti-depressant activity of the leaves extract of Zanthoxylum armatum using forced swim test and tail suspension test (TST) on Swiss albino mice. MATERIAL AND METHODS The anti-depressant activity of the leaves of Zanthoxylum armatum was assessed using chronic unpredictable mild-stress (CUMS) induced depression in mice. The animals were treated with the methanolic extract of leaves of Zanthoxylum armatum orally at two doses of 100, 200 mg/kg body weight for eight days after (CUMS) induced depression in mice. RESULTS The data were analyzed by one-way ANOVA followed by tukey multiple comparison test. The leaves extract presented significant antidepressant activity in mice (p<0.05), CONCLUSION The results demonstrate that methanolic extract of leaves of Zanthoxylum armatum has got significant antidepressant activity.

Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in mice

2016 ◽  
Vol 27 (6) ◽  
Author(s):  
Proteesh Rana ◽  
Amit K. Sharma ◽  
Smita Jain ◽  
Pravin Deshmukh ◽  
S.K. Bhattacharya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Thiobarbituric Acid ◽  
Interferon Γ ◽  
Saline Group ◽  
Kynurenine Pathway ◽  
Bacillus Calmette Guerin ◽  
Protein Thiols ◽  
The Brain

AbstractBackground:The inflammatory response system has been implicated in the pathophysiology of major depression. The pro-inflammatory cytokines like interferon-γ induce the enzyme indoleamine-2,3-dioxygenase (IDO) of the kynurenine pathway of tryptophan metabolism. The induction of IDO reduces the availability of tryptophan for serotonin synthesis. Furthermore, the metabolites of kynurenine pathway have neurotoxic property, which along with decreased serotonin may account for depression-like illness.Methods:The aim of this study was to compare the effects of treatment with fluoxetine and 1-methyl-L-tryptophan (1-MT) on Bacillus Calmette-Guerin (BCG)-induced inflammatory model of depression in mice. Behavioral tests included locomotor activity, forced swim test (FST) and tail suspension test (TST). Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in homogenized whole brain samples. Comet assays were performed to assess neurotoxicity.Results:The results of this study demonstrate that BCG treatment resulted in an increase in duration of immobility in FST and TST as compared to the saline group. Further, it produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. The hippocampal tissue from BCG group had significantly more comet cells than the saline group. 1-MT and fluoxetine were able to reverse the BCG-induced depression-like behavior and the derangement in oxidative stress parameters. Fluoxetine and 1-MT also reversed the BCG-induced neurotoxicity in such mice.Conclusions:1-Methyl-L-tryptophan exhibits antidepressant-like effect comparable to that of fluoxetine in treating BCG-induced depression-like behavior in mice.

Effect of dialkyl- [2-(1-oxa-3,4,9-triaza-fluoren-2-yl-methoxy)ethyl] amines on biogenic amines: new potential antidepressants

2012 ◽  
Vol 90 (12) ◽  
pp. 1585-1590
Author(s):  
Akena Venkatesham ◽  
J. Venkateshwar Rao ◽  
K. Vijay Kumar ◽  
M. Sarangapani ◽  
Krishna Devarakonda
Keyword(s):  
Biogenic Amines ◽  
Forced Swim Test ◽  
Chronic Administration ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Control Group ◽  
Stress Model ◽  
Chronic Unpredictable Stress ◽  
The Brain

A thorough survey of the literature has revealed that indole derivatives have shown various central nervous system activities. This study aims to evaluate the antidepressant activity of the newly synthesized dialkyl- [2-(1-oxa-3,4,9-triaza-fluoren-2-yl-methoxy)ethyl] amines and their effect on biogenic amines. In this study, the synthesized compounds were assessed by in-vivo antidepressant models, by forced swim test and tail suspension test in mice and effect of synthesized compounds on biogenic amines in brain in a chronic unpredictable stress model. The test compounds have demonstrated significant (P < 0.05) reduced immobility duration in mice when compared with the control group animals. The reduced immobility displayed by mice indicates potential antidepressant activity. In this study, chronic unpredictable stress led to decreased monoamine levels in the cortex and hippocampus regions of the brain. With chronic administration of the investigated compounds there is an increased in monoamines in the brain, in the chronic unpredictable stress model. Decreased levels of monoamines induced by the chronic unpredictable stress induced model of depression, were normalized by treatment with the test compounds, which indicates potential antidepressant activity.

scholarly journals Influence of the endocannabinoid system on the antidepressant activity of bupropion and moclobemide in the behavioural tests in mice

2020 ◽  
Vol 72 (6) ◽  
pp. 1562-1572
Author(s):  
Ewa Poleszak ◽  
Sylwia Wośko ◽  
Karolina Sławińska ◽  
Elżbieta Wyska ◽  
Aleksandra Szopa ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Antidepressant Drugs ◽  
Endocannabinoid System ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Cellular Level ◽  
Hplc Method ◽  
Receptor Function ◽  
Receptor Ligands ◽  
Behavioural Tests

Abstract Background Though there are several classes of antidepressant drugs available on the pharmaceutical market, depression that affects globally over 320 million people is still undertreated. Scientists have made attempts to develop novel therapeutical strategies to maximize effectiveness of therapy and minimize undesired reactions. One of the ideas is use of either dual-action agents or combined administration of two substances that affect diverse neurotransmissions. Thus, we investigated whether the selected CB receptor ligands (oleamide, AM251, JWH133, and AM630) can have an impact on the activity of bupropion and moclobemide. Bupropion belongs to the dual acting drugs, whereas moclobemide is an inhibitor of monoamine oxidase. Methods The mice forced swim test and the tail suspension test were applied in order to determine the potential antidepressant-like activity, whereas the HPLC method was used in order to assess the brain concentrations of the tested antidepressants. Results An intraperitoneal injection of sub-effective doses of oleamide (5 mg/kg), AM251 (0.25 mg/kg), and AM630 (0.25 mg/kg) increased activity of bupropion (10 mg/kg) in both behavioural tests. Effects of moclobemide (1.5 mg/kg) were potentiated only by AM251. These results were not influenced by the hypo- or hyperlocomotion of animals. Conclusion The outcomes of the present study revealed that particularly activation or inhibition of the CB1 receptor function may augment the antidepressant activity of bupropion, whereas only inhibition of the CB1 receptor function manages to increase activity of moclobemide. Most probably, an interplay between CB receptor ligands and bupropion or moclobemide takes place at the cellular level.

Use of Protein a Conjugated to Peroxidase to Localize Immunoglobulin G in SSPE Ferret Brain

1982 ◽  
Vol 40 ◽  
pp. 350-351
Author(s):  
Hannah R. Brown ◽  
Anthony F. Nostro ◽  
Halldor Thormar
Keyword(s):  
Immunoglobulin G ◽  
Human Disease ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Inflammatory Lesions ◽  
Sspe Virus ◽  
Specific Immunoglobulin ◽  
Antibody Titers ◽  
The Brain

Subacute sclerosing panencephalitis (SSPE) is a slowly progressing disease of the CNS in children which is caused by measles virus. Ferrets immunized with measles virus prior to inoculation with the cell associated, syncytiogenic D.R. strain of SSPE virus exhibit characteristics very similar to the human disease. Measles virus nucleocapsids are present, high measles antibody titers are found in the sera and inflammatory lesions are prominent in the brains. Measles virus specific immunoglobulin G (IgG) is present in the brain,and IgG/ albumin ratios indicate that the antibodies are synthesized within the CNS.

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

Astaxanthin, the Natural Antioxidant, Reduces Reserpine Induced Depression in Mice

2020 ◽  
Vol 16 (9) ◽  
pp. 1319-1327
Author(s):  
Ferdous Khan ◽  
Syed A. Kuddus ◽  
Md. H. Shohag ◽  
Hasan M. Reza ◽  
Murad Hossain
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reduced Glutathione ◽  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Glutathione Depletion ◽  
Swim Test ◽  
Stress Markers ◽  
Immobility Time ◽  
Biochemical Level

Background: An imbalance between pro-oxidants and antioxidants determines the level of oxidative stress which is implicated in the etiopathogenesis of various neuropsychiatric disorders including depression. Therefore, treatment with antioxidants could potentially improve the balance between pro-oxidants and antioxidants. Objective: The objective of this study was to evaluate the ability of astaxanthin, a potential antioxidant, to reduce reserpine-induced depression in BALB/c mice (Mus musculus). Methods: On the behavioral level, antidepressant property of astaxanthin (50 mg/kg, orally) on reserpine (2 mg/kg, subcutaneously) induced depressed mice was evaluated by Forced Swim Test (FST) and Tail Suspension Test (TST). In the biochemical level, the ability of astaxanthin to mitigate reserpine-induced oxidative stress was evaluated by the measurement of Malondialdehyde (MDA) and nitric oxide (NO) in brain, liver and plasma samples. On the other hand, the efficiency of astaxanthin to replenish glutathione depletion and antioxidant enzyme activity augmentation in the same samples were also investigated. Results: Astaxanthin was able to lower reserpine induced immobility time significantly (p<0.05) in FST and TST. Mice treated with astaxanthin showed significantly (p<0.05) low level of oxidative stress markers such as Malondialdehyde (MDA), Nitric Oxide (NO). Consistently, the level of reduced Glutathione (GSH), and the activity of Superoxide Dismutase (SOD) and catalase were augmented due to the oral administration of astaxanthin. Conclusion: This study suggests that astaxanthin reduces reserpine-induced oxidative stress and therefore might be effective in treating oxidative stress associated depression.

scholarly journals Differential expression of TgMIC1 in isolates of Chinese 1 Toxoplasma with different virulence

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yang Wang ◽  
Chengjian Han ◽  
Rongsheng zhou ◽  
Jinjin Zhu ◽  
Famin Zhang ◽  
...  
Keyword(s):  
Differential Expression ◽  
Rna Sequencing ◽  
Polyclonal Antibody ◽  
Protein Level ◽  
Polyclonal Antibodies ◽  
Mrna Levels ◽  
Quantitative Real Time Pcr ◽  
Sequencing Data ◽  
Predominant Genotype ◽  
High Virulence

Abstract Background The predominant genotype of Toxoplasma in China is the Chinese 1 (ToxoDB#9) lineage. TgCtwh3 and TgCtwh6 are two representative strains of Chinese 1, exhibiting high and low virulence to mice, respectively. Little is known regarding the virulence mechanism of this non-classical genotype. Our previous RNA sequencing data revealed differential mRNA levels of TgMIC1 in TgCtwh3 and TgCtwh6. We aim to further confirm the differential expression of TgMIC1 and its significance in this atypical genotype. Methods Quantitative real-time PCR was used to verify the RNA sequencing data; then, polyclonal antibodies against TgMIC1 were prepared and identified. Moreover, the invasion and proliferation of the parasite in HFF cells were observed after treatment with TgMIC1 polyclonal antibody or not. Results The data showed that the protein level of TgMIC1 was significantly higher in high-virulence strain TgCtwh3 than in low-virulence strain TgCtwh6 and that the invasion and proliferation of TgCtwh3 were inhibited by TgMIC1 polyclonal antibody. Conclusion Differential expression of TgMIC1 in TgCtwh3 and TgCtwh6 may explain, at least partly, the virulence mechanism of this atypical genotype.

scholarly journals Aicardi-Goutières syndrome-associated mutation at ADAR1 gene locus activates innate immune response in mouse brain

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xinfeng Guo ◽  
Clayton A. Wiley ◽  
Richard A. Steinman ◽  
Yi Sheng ◽  
Beihong Ji ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Rna Editing ◽  
Mouse Brain ◽  
Mutant Mouse ◽  
Cell Types ◽  
Mutant Mice ◽  
Blue Staining ◽  
Sequencing Analysis ◽  
Elevated Type ◽  
The Brain

Abstract Background Aicardi-Goutières syndrome (AGS) is a severe infant or juvenile-onset autoimmune disease characterized by inflammatory encephalopathy with an elevated type 1 interferon-stimulated gene (ISG) expression signature in the brain. Mutations in seven different protein-coding genes, all linked to DNA/RNA metabolism or sensing, have been identified in AGS patients, but none of them has been demonstrated to activate the IFN pathway in the brain of an animal. The molecular mechanism of inflammatory encephalopathy in AGS has not been well defined. Adenosine Deaminase Acting on RNA 1 (ADAR1) is one of the AGS-associated genes. It carries out A-to-I RNA editing that converts adenosine to inosine at double-stranded RNA regions. Whether an AGS-associated mutation in ADAR1 activates the IFN pathway and causes autoimmune pathogenesis in the brain is yet to be determined. Methods Mutations in the ADAR1 gene found in AGS patients were introduced into the mouse genome via CRISPR/Cas9 technology. Molecular activities of the specific p.K999N mutation were investigated by measuring the RNA editing levels in brain mRNA substrates of ADAR1 through RNA sequencing analysis. IFN pathway activation in the brain was assessed by measuring ISG expression at the mRNA and protein level through real-time RT-PCR and Luminex assays, respectively. The locations in the brain and neural cell types that express ISGs were determined by RNA in situ hybridization (ISH). Potential AGS-related brain morphologic changes were assessed with immunohistological analysis. Von Kossa and Luxol Fast Blue staining was performed on brain tissue to assess calcification and myelin, respectively. Results Mice bearing the ADAR1 p.K999N were viable though smaller than wild type sibs. RNA sequencing analysis of neuron-specific RNA substrates revealed altered RNA editing activities of the mutant ADAR1 protein. Mutant mice exhibited dramatically elevated levels of multiple ISGs within the brain. RNA ISH of brain sections showed selective activation of ISG expression in neurons and microglia in a patchy pattern. ISG-15 mRNA was upregulated in ADAR1 mutant brain neurons whereas CXCL10 mRNA was elevated in adjacent astroglia. No calcification or gliosis was detected in the mutant brain. Conclusions We demonstrated that an AGS-associated mutation in ADAR1, specifically the p.K999N mutation, activates the IFN pathway in the mouse brain. The ADAR1 p.K999N mutant mouse replicates aspects of the brain interferonopathy of AGS. Neurons and microglia express different ISGs. Basal ganglia calcification and leukodystrophy seen in AGS patients were not observed in K999N mutant mice, indicating that development of the full clinical phenotype may need an additional stimulus besides AGS mutations. This mutant mouse presents a robust tool for the investigation of AGS and neuroinflammatory diseases including the modeling of potential “second hits” that enable severe phenotypes of clinically variable diseases.

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