Simvastatin exerts antidepressant-like activity in mouse forced swimming test: Role of NO-cGMP-KATP channels pathway and PPAR-gamma receptors

Naserzadeh, Reza; Abad, Niloofar; Ghorbanzadeh, Behnam; Dolatshahi, Mojtaba; Mansouri, Mohammad Taghi

doi:10.1016/j.pbb.2019.03.002

Cited by 23 publications

(9 citation statements)

References 41 publications

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“…The FST was performed according to a previously reported method with slight modifications. 34 The rats were placed in a bucket (50 cm high × 25 cm in diameter) filled with water (20-22 °C) to a depth of 35 cm. The rats were allowed to swim for 6 min, and immobility was recorded during the last 4 min.…”

Section: Fstmentioning

confidence: 99%

<p>Electroacupuncture Relieves LPS-Induced Depression-Like Behaviour in Rats Through IDO-Mediated Tryptophan-Degrading Pathway</p>

Zhang¹,

Liu²,

Gao³

et al. 2020

NDT

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Background: Neuroinflammation is an important pathological mechanism of depression that leads to an increase in indoleamine-2,3-dioxygenase (IDO) activity and NMDAR activation. This study aimed to observe the effects of electroacupuncture on depressionlike behaviour in lipopolysaccharide (LPS)-treated rats and the underlying mechanism. Methods: Wistar rats were intraperitoneally administered LPS (0.5 mg/kg) for 7 consecutive days to establish a depression model. Electroacupuncture treatment was administered 1 hour after daily LPS injection. The open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT) were used to evaluate the depressive-like behaviours. IL-1β, IL-6, and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA); Trp, 5-hydroxytryptamine (5-HT), kynurenine (Kyn) and quinolinic acid (Quin) were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry; and N-methyl-D-aspartate receptor (NMDAR) protein and mRNA were assessed by Western blot and real-time qPCR. Results: The results showed that electroacupuncture treatment successfully corrected LPSinduced depressive-like behaviour, reduced the inflammatory factor (IL-1β, IL-6 and TNF-α) levels in the blood and hippocampus, prevented IDO over-activation and recovered NR2B expression after challenge by LPS. Conclusion: Electroacupuncture treatment provided protection against LPS-induced depressive-like behaviour, and the associated mechanisms may be related to inhibiting the inflammatory response, regulating the IDO-mediated tryptophan-degrading pathway, and inhibiting NR2B activation.

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Section: Fstmentioning

confidence: 99%

<p>Electroacupuncture Relieves LPS-Induced Depression-Like Behaviour in Rats Through IDO-Mediated Tryptophan-Degrading Pathway</p>

Zhang¹,

Liu²,

Gao³

et al. 2020

NDT

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“…The depressive and anxiety behaviours caused in rats by chronic mild stress ( 45 ) or high-fat diet ( 46 ) were counteracted by statins, similarly to antidepressant medications. The depressogenic effect of reactive oxygen species (ROS) in the brain ( 47 ) could be reduced by statins both directly ( 48 ) and via peroxisome proliferator-activated receptor (PPAR)-γ activity and decreased nitrous oxide (NO) levels ( 49 , 50 ) according to animal studies. Furthermore, glutamatergic N-methyl-D-aspartate (NMDA)-induced neuronal damage ( 51 ), whose modulation is associated to the mechanism of action of ketamine ( 52 ), is similarly affected by statins via direct ( 53 ) and PI3K/AKT/GSK3b/mTOR-mediated ( 54 ) antagonism.…”

Section: Introductionmentioning

confidence: 99%

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

et al. 2021

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Background: Depression is a leading cause of disability, burdened by high levels of non-response to conventional antidepressants. Novel therapeutic strategies targeting non-monoaminergic pathways are sorely needed. The widely available and safe statins have several putative mechanisms of action, especially anti-inflammatory, which make them ideal candidates for repurposing in the treatment of depression. A large number of articles has been published on this topic. The aim of this study is to assess this literature according to evidence-based medicine principles to inform clinical practise and research.Methods: We performed a systematic review of the electronic databases MEDLINE, CENTRAL, Web of Science, CINAHL, and ClinicalTrials.gov, and an unstructured Google Scholar and manual search, until the 9th of April 2021, for all types of clinical studies assessing the effects of statins in depression.Results: Seventy-two studies were retrieved that investigated the effects of statins on the risk of developing depression or on depressive symptoms in both depressed and non-depressed populations. Fifteen studies specifically addressed the effects of statins on inflammatory-related symptoms of anhedonia, psychomotor retardation, anxiety, and sleep disturbances in depression. Most studies suggested a positive effect of statins on the occurrence and severity of depression, with fewer studies showing no effect, while a minority indicated some negative effects.Limitations: We provide a narrative report on all the included studies but did not perform any quantitative analysis, which limits the strength of our conclusions.Conclusions: Robust evidence indicates that statins are unlikely to lead to depressive symptoms in the general population. Promising data suggest a potential role for statins in the treatment of depression. Further clinical studies are needed, especially in specific subgroups of patients identified by pre-treatment assessments of inflammatory and lipid profiles.

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“…The used drugs were dissolved or suspended in normal saline (0.9% NaCl) and injected in a volume of 10 ml/kg. The selection of doses and route of administration were based on previous studies and also experiments in our laboratory ( Mansouri et al, 2018 ; Naserzadeh et al, 2019 ; Dejban et al, 2020 ; Ajaman et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

The effect of montelukast, a leukotriene receptor antagonist, on the acetic acid-induced model of colitis in rats: Involvement of NO-cGMP-KATP channels pathway

et al. 2022

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Inflammatory bowel disease is a chronic autoimmune disorder that may involve entire gastrointestinal tract. The leukotrienes have a role as mediators in the pathophysiology of colitis. Here, we investigated the effect of a leukotriene receptor antagonist, montelukast, and also the role of the NO-cGMP-KATP channel pathway in acetic acid-induced colitis. Rectal administration of acetic acid (4%) was used for induction of colitis in rats. To investigate our hypothesis, the rats were intraperitoneally pre-treated with L-NAME (NOS inhibitor), L-arginine, sildenafil, methylene blue, glibenclamide, or diazoxide 15 min before treatment with montelukast (5–20 mg/kg, i. p.), for three consecutive days. Then, microscopic, macroscopic, and inflammatory parameters were evaluated. Montelukast reduced the microscopic and macroscopic damage induced by acetic acid. Montelukast also reduced the level of IL-1β and TNF-α. We also showed that the effects of montelukast were significantly attenuated by L-NAME, methylene blue (guanylate cyclase inhibitor), and an ATP-sensitive potassium channel blocker (glibenclamide). Also, the administration of L-arginine, sildenafil, and diazoxide before montelukast produced protective effect. In conclusion, the pathway of the NO-cGMP-KATP channel is involved in the protective effect of montelukast in acetic acid-induced colonic tissue damage.

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Simvastatin exerts antidepressant-like activity in mouse forced swimming test: Role of NO-cGMP-KATP channels pathway and PPAR-gamma receptors

Cited by 23 publications

References 41 publications

<p>Electroacupuncture Relieves LPS-Induced Depression-Like Behaviour in Rats Through IDO-Mediated Tryptophan-Degrading Pathway</p>

<p>Electroacupuncture Relieves LPS-Induced Depression-Like Behaviour in Rats Through IDO-Mediated Tryptophan-Degrading Pathway</p>

Statins in Depression: An Evidence-Based Overview of Mechanisms and Clinical Studies

The effect of montelukast, a leukotriene receptor antagonist, on the acetic acid-induced model of colitis in rats: Involvement of NO-cGMP-KATP channels pathway

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