Muscone Ameliorates LPS-Induced Depressive-Like Behaviors and Inhibits Neuroinflammation in Prefrontal Cortex of Mice

Depression is partially caused by inflammation in the central nervous system. Early study demonstrated that musk, glandular secretion from male musk deer, exerted an antidepressant-like effect. The aim of this study was to investigate if muscone, a bioactive ingredient in musk, could ameliorate neuroinflammation and depressive-like behaviors as well as explore the potential action mechanism. Mice were intraperitoneally (i.p.) injected with muscone for 2 weeks prior to administration of lipopolysaccharides (LPS, 1[Formula: see text]mg/kg, i.p.). Pre-treatment with muscone reversed the LPS-induced decrease in body weight within 24[Formula: see text]h and ameliorated depressive-like behaviors shown by sucrose preference, tail suspension test, and forced swimming test. LPS-induced activation of microglial cells and elevation in expression of inflammatory cytokines including IL-1[Formula: see text], RANTES, and MCP-1 in the prefrontal cortex of mice were effectively abrogated by muscone, which significantly down-regulated expression of TLR4, MyD88, Caspase-1, NLRP3, renin, and Ang II. In addition, treatment of BV2 microglia cells with muscone markedly attenuated the LPS-induced rise in protein expression of TLR4, Ang II, and IL-1[Formula: see text]. This study revealed that muscone could ameliorate LPS-induced depressive-like behaviors by repressing neuroinflammation in the prefrontal cortex of mice caused by its suppression on microglia activation and production of inflammatory cytokines via acting on TLR4 pathway and RAS cascade.

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ANTI-DEPRESSANT EFFECT OF CEFTRIAXONE IN FORCED SWIMMING TEST AND IN TAIL SUSPENSION TEST IN MICE

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i11.14466 ◽

2016 ◽

Vol 8 (11) ◽

pp. 191 ◽

Cited By ~ 2

Author(s):

Ajoy Borah ◽

Binita Singha ◽

Swopna Phukan

Keyword(s):

Forced Swimming Test ◽

Antidepressant Activity ◽

Tail Suspension Test ◽

Forced Swimming ◽

Antidepressant Effect ◽

Tail Suspension ◽

Neuroprotective Effects ◽

The Central Nervous System ◽

Swimming Test ◽

Suspension Test

Objective: Depression is a major psychiatric disorder affecting nearly 350 million people worldwide and imposes a substantial health burden on the society. Ceftriaxone has demonstrated neuroprotective effects in animals. It has also undergone trials as a treatment option for amyotrophic lateral sclerosis. This study was therefore undertaken to evaluate the antidepressant-like effect of ceftriaxone in mice.Methods: Ceftriaxone was administered at three different doses (0.130, 0.195 and 0.260g/kg) to Swiss albino mice of either sex by intra peritoneal (i. p.) route. The period of immobility in control and drug-treated mice were recorded in forced swimming test (FST) and tail suspension test (TST). The antidepressant effect of ceftriaxone indicated by the decrease in duration of immobility was compared to that of fluoxetine (0.020 g/kg, i. p.).Results: Ceftriaxone decreased the duration of immobility in mice. It showed a significant dose-dependent antidepressant effect. The antidepressant effect of 0.260g/kg of ceftriaxone was comparable to that of fluoxetine in the TST but not in the FST.Conclusion: The results of the present study indicate antidepressant activity of Ceftriaxone. The study shows that ceftriaxone has additional action on the central nervous system other than neuroprotection. Ceftriaxone therapy in cases of encephalomeningitis and in various cases of hemorrhages in the brain can, therefore, prevent the development of depression in future

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Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

BioMed Research International ◽

10.1155/2015/159015 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 18

Author(s):

Chia-Yu Chang ◽

How-Ran Guo ◽

Wan-Chen Tsai ◽

Kai-Lin Yang ◽

Li-Chuan Lin ◽

...

Keyword(s):

Drinking Water ◽

Prefrontal Cortex ◽

Mouse Model ◽

Arsenic Exposure ◽

Tail Suspension Test ◽

Behavioral Disturbances ◽

Chemically Induced ◽

Contaminated Drinking Water ◽

Swimming Test ◽

Underlying Mechanisms

Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water) on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM) and open field test (OFT) in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST) and forced swimming test (FST) in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

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Tetragonia tetragonioides Relieves Depressive-Like Behavior through the Restoration of Glial Loss in the Prefrontal Cortex

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8888841 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Yujin Choi ◽

Yunna Kim ◽

Hwa-Young Lee ◽

Seung-Hun Cho

Keyword(s):

Prefrontal Cortex ◽

Preference Test ◽

Tail Suspension Test ◽

Antidepressant Effect ◽

Antidepressant Agent ◽

Immobility Time ◽

Swimming Test ◽

Asian Pacific ◽

Sucrose Preference Test ◽

Tetragonia Tetragonioides

Tetragonia tetragonioides, which is a halophyte and grows widely in Asian-Pacific regions, has been used for the treatment of digestive disorders in traditional oriental medicine. This study examined the potential antidepressant effect of Tetragonia tetragonioides in an astroglial degeneration model of depression, which was established based on the postmortem study of depressive patients’ brain presenting diminished astrocytes in the prefrontal cortex. C57BL/6 male mice were exposed to glial ablation in the prefrontal cortex by the administration of the gliotoxin, L-alpha-aminoadipic acid (L-AAA) to induce depression. Tetragonia tetragonioides at doses of 100 mg/kg and 300 mg/kg, imipramine at a dose of 15 mg/kg, and distilled water were orally administrated to mice for 18 days. Behavioral tests including the open field test (OFT), sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST) were carried out after 2 days of L-AAA injection. The expression levels of GFAP and NeuN in the prefrontal cortex were determined by immunohistochemistry. Mice subjected to glial ablation in the prefrontal cortex displayed decreased sucrose consumption in SPT and increased immobility time in FST and TST. Treatment with imipramine and Tetragonia tetragonioides remarkably ameliorated the behavioral despair induced by L-AAA. In addition, immunohistochemistry analysis showed that treatment with Tetragonia tetragonioides significantly restored the glial loss as indicated by the elevated GFAP expression level. These findings suggest that Tetragonia tetragonioides exerts an antidepressant effect through the restoration of glial loss under conditions of depression and can be a candidate for an antidepressant agent.

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RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders

Current Medicinal Chemistry ◽

10.2174/0929867325666180226102358 ◽

2018 ◽

Vol 25 (28) ◽

pp. 3333-3352 ◽

Cited By ~ 21

Author(s):

Natalia Pessoa Rocha ◽

Ana Cristina Simoes e Silva ◽

Thiago Ruiz Rodrigues Prestes ◽

Victor Feracin ◽

Caroline Amaral Machado ◽

...

Keyword(s):

Blood Pressure ◽

Central Nervous System ◽

Nervous System ◽

Therapeutic Potential ◽

Neuropsychiatric Disorders ◽

Extensive Literature ◽

Ang Ii ◽

Mas Receptor ◽

The Central Nervous System ◽

The Brain

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

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Some Aspects of the Psychopharmacological Activity of Maprotiline (Ludiomil®): Effects of Single and Repeated Treatments

Journal of International Medical Research ◽

10.1177/030006057800600601 ◽

1978 ◽

Vol 6 (6) ◽

pp. 421-429 ◽

Cited By ~ 9

Author(s):

A Delini-Stula ◽

E Radeke ◽

A Vassout

Keyword(s):

Nervous System ◽

Chronic Treatment ◽

Conditioned Fear ◽

Conditioned Avoidance ◽

Repeated Treatment ◽

Antidepressant Effects ◽

The Central Nervous System ◽

Pre Treatment ◽

High Doses ◽

Psychopharmacological Activity

Three different aspects of the psychopharmacological activity of the antidepressant maprotiline were investigated: its influence on serotoninergic functions the effects produced by chronic treatment its central nervous depressant and anxiolytic properties. Study of the effects of maprotiline on 5-HTP-induced head-twitch in mice pre-treated with pargyline or on hyperpyrexia in rats provided no evidence that the drug interferes with serotonin-mediated functions in the central nervous system even after quite high doses. These findings corroborate the results of extensive neurobiochemical investigations, which failed to demonstrate any influence of maprotiline on the metabolism of serotonin. Chronic studies showed that classical effects of maprotiline such as antagonism against reserpine-induced ptosis or tetrabenazine-induced catalepsy do not change in their intensity after daily administration of the drugs in a dose of 30 mg/kg p.o.for 11 days. A new component of the action of the compound, not detectable after one single dose, seems to appear, however, after repeated treatment (8 days). This effect is manifested in the restoration of conditioned avoidance behaviour after its suppression by pre-treatment with reserpine. The same effect is produced by imipramine. It is suggested that this restorative effect may be due to an additional activation of the dopaminergic nervous system and may have a bearing on the appearance of clinical antidepressant effects. Maprotiline was found to potentiate central nervous depressant effects of drugs like chlorpromazine, phenobarbitone and propranolol. This affords further confirmation that, in addition to its antidepressant qualities, it possesses sedative actions. An anxiolytic component was also demonstrated in rats in which maprotiline suppressed the conditioned, fear-induced rise in body-temperature.

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Effects of ketamine on lipopolysaccharide-induced depressive-like behavior and the expression of inflammatory cytokines in the rat prefrontal cortex

Molecular Medicine Reports ◽

10.3892/mmr.2013.1600 ◽

2013 ◽

Vol 8 (3) ◽

pp. 887-890 ◽

Cited By ~ 14

Author(s):

CHUN YANG ◽

JIANG SHEN ◽

TAO HONG ◽

TING-TING HU ◽

ZHANG-JUN LI ◽

...

Keyword(s):

Prefrontal Cortex ◽

Inflammatory Cytokines

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Nitric oxide mediates the antidepressant-like effect of modafinil in mouse forced swimming and tail suspension tests

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0021 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Hossein Omidi-Ardali ◽

Abolfazl Ghasemi Badi ◽

Elham Saghaei ◽

Hossein Amini-Khoei

Keyword(s):

Nitric Oxide ◽

Effective Dose ◽

Animal Studies ◽

Tail Suspension Test ◽

Forced Swimming ◽

Antidepressant Effect ◽

Tail Suspension ◽

Immobility Time ◽

Swimming Test ◽

Underlying Mechanisms

AbstractObjectivesPrevious studies have suggested antidepressant properties for modafinil; however, the underlying mechanisms mediating the antidepressant effect of modafinil have not been well recognized in clinical and animal studies. Nitric oxide (NO) is involved in the pathophysiology of depression. We attempted to investigate the possible role of NO in the antidepressant-like effect of modafinil in mouse forced swimming test (FST) and tail suspension test (TST).MethodsThe antidepressant-like effect of modafinil (25, 50 and 75 mg/kg), alone and in combination with l-arginine, l-arg, (100 mg/kg) and NG-l-arginine methyl ester, l-NAME (5 mg/kg), was evaluated using FST and TST. Following behavioral tests, the hippocampi were dissected out to measure nitrite levels.ResultsFindings suggested that administration of modafinil at doses of 50 and 75 mg/kg significantly reduced immobility time in the FST and TST. Furthermore, administration of l-arg and l-NAME increased and decreased, respectively, the immobility time in the FST and TST. We showed that co-administration of a sub-effective dose of modafinil (25 mg/kg) plus l-NAME potentiated the antidepressant-like effect of the sub-effective dose of modafinil. In addition, co-treatment of an effective dose of modafinil (75 mg/kg) with l-arg attenuated the antidepressant-like effect of the effective dose of modafinil. We showed that the antidepressant-like effect of modafinil is associated with decreased nitrite levels in the hippocampus.ConclusionsOur findings for the first time support that the modulation of NO, partially at least, is involved in the antidepressant-like effect of modafinil in mouse FST and TST.

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Abstract 51: Thymosin β4 Targets Wisp1 to Protect Cardiomyocytes in AngII- induced Cardiac Hypertrophy

Circulation Research ◽

10.1161/res.117.suppl_1.51 ◽

2015 ◽

Vol 117 (suppl_1) ◽

Author(s):

Sudhiranjan Gupta ◽

Li Li ◽

Rakesh Guleria ◽

Kenneth M Baker

Keyword(s):

Cardiac Hypertrophy ◽

Fluorescent Microscopy ◽

Marker Genes ◽

Protective Mechanism ◽

Ang Ii ◽

Hypertrophic Response ◽

Antiapoptotic Proteins ◽

Neonatal Cardiomyocytes ◽

Cell Proliferation And Differentiation ◽

Pre Treatment

Background: Thymosin beta-4 (Tβ4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. However, the role of Tβ4 in cardiomyocytes hypertrophy is currently unknown. The purpose of this study is to dissect the cardio-protective mechanism of Tβ4 in Ang II induced cardiac hypertrophy. Methods: Rat neonatal cardiomyocytes with or without Tβ4 pretreatment were stimulated with Ang II and expression of cell sizes, hypertrophy marker genes and Wnt signaling components was evaluated by quantitative real-time PCR, western blotting and fluorescent microscopy. Selected target gene Wisp-1 was either overexpressed or silenced by siRNA transfections in neonatal cardiomyocytes and effect of Tβ4 in Ang II-induced cardiac hypertrophy was evaluated. Results: Pre-treatment of Tβ4 resulted in reduction of cell sizes, hypertrophy marker genes and WNT-associated gene expression and levels induced by Ang II in cardiomyocytes. Tβ4 pretreatment also resulted in an increase in the expression of antiapoptotic proteins and reduction of Bax/BCl 2 ratio in the cardiomyocytes. Wisp-1 overexpression promotes cardiac hypertrophy and was reversed by pretreatment with Tβ4. Knocking down of Wisp1 partly rescue the cells from hypertrophic response after Tβ4 treatment. Conclusion: This is the first report that demonstrates the effect of Tβ4 on cardiomyocytes hypertrophy and its capability to selectively target Wisp-1 in neonatal cardiomyocytes thus preventing cell death, thereby, protecting the myocardium. Wisp-1 promotes the cardiac hypertrophy which was prevented by Tβ4 treatment.

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Daphnetin Ameliorates Corticosterone-Induced Depressive-Like Behavior and Oxidative Stress in Mice Via Nuclear Factor Erythroid 2-Related Factor/Heme Oxygenase-1 Pathway

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:470-476 ◽

2021 ◽

Vol 19 (4) ◽

pp. 470-476

Author(s):

Chao Liu ◽

Chao Liang ◽

Jie Huang

Keyword(s):

Oxidative Stress ◽

Consumption Rate ◽

Tail Suspension Test ◽

Protein Carbonyl ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Sucrose Consumption ◽

Markers Of Oxidative Stress ◽

Swimming Test ◽

And Oxidative Stress

We have investigated the effect of daphnetin on depressive-like behavior and oxidative stress caused by corticosterone in mice. To this end, we have analyzed the effect of corticosterone alone and combination of corticosterone and daphnetin on three behavioral indices of depressive-like behavior - sucrose consumption rate, forced swimming test, and tail suspension test as well as biochemical markers of oxidative stress - malondialdehyde, nitrite, protein carbonyl, nonprotein sulfhydryl and glutathione contents as well as hippocampal cell apoptosis. The results support the conclusion that daphnetin diminished corticosterone induced depressive like behavior and oxidative stress by activating Nrf2/HO-1 pathway.

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