Effects of Vortioxetine on depression model rats and expression of BDNF and Trk B in hippocampus

Sun, Baomin; Lv, Yanhua; Xu, Haowen; Qi, Chenze; Li, Cuiping; Liu, Pengfei

doi:10.3892/etm.2020.9026

Cited by 12 publications

(15 citation statements)

References 31 publications

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“…Depression is considered a common mental illness leading to upset or anxiety, with a high incidence rate in the world. Depression may lead to suicidal thoughts and behavior, or mental illness manifestations, for example, fantasy or delusion (Sun et al, 2020). The World Health Organization statistics show that more than three hundred million people around the world (4.4%) endure from depression (World Health Organization (WHO)., 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Brain-derived neurotrophic factor (BDNF) is the most prominent neurotrophic factor which shows decreased expression and function with depression and reveals an improvement by the antidepressant therapy (Zhou et al, 2017;Sun et al, 2020). The BDNF protein along with mRNA in the hippocampus of mice with depression was significantly reduced by learned helplessness (Su et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Rivaroxaban Modulates TLR4/Myd88/NF-Kβ Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression

et al. 2021

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Depression is a common mental illness leading to upset or anxiety, with a high incidence rate in the world. Depression can lead to suicidal thoughts and behavior. The present study aimed to evaluate the effect of the direct oral anticoagulant rivaroxaban (RVX), in the model of depression induced by chronic unpredicted mild stress (CUMS) in rats. Fifty-six male Wister rats were randomly divided into seven experimental groups (8 rats/group); Group 1: Control group given vehicle per oral (p.o.), Group 2: RVXL-control group (received rivaroxaban 20 mg/kg/day, p.o..), Group 3: RVXH-control group (received rivaroxaban 30 mg/kg/day, p.o.), Group 4: chronic unpredictable mild stress (CUMS) group, Group 5: FLX-treated CUMS group (received fluoxetine 10 mg/kg/day, p.o..), Group 6: RVXL-treated CUMS group (received rivaroxaban 20 mg/kg/day, p.o.), and Group 7: RVXH-treated CUMS group (received rivaroxaban 30 mg/kg/day, p.o.). The rats received the drugs from the first day of the experiment and continued till 4 weeks—the duration of the study. The following were measured: monoamine neurotransmitters, malondialdehyde (MDA), total nitrite/nitrate (NOx), reduced glutathione (GSH), superoxide dismutase (SOD), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor‐kappa B (NF‐κB), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor-A (VEGF-A). A forced swimming test (FST) was done. Furthermore, histological changes and glial fibrillary acidic protein (GFAP) immunoexpression were evaluated. CUMS showed a significant decrease in hypothalamic neurotransmitters, hippocampal GSH, SOD, BNDF, and VEGF-A with a significant increase in hippocampal MDA, NOx, NF-kβ, Myd88, TLR4, TNF-α, and GFAP immunoexpression. RVX showed significant improvement in all parameters (p-value < 0.0001). In conclusion, RVX in a dose-dependent manner possesses potent ameliorative effects against depression by reducing the oxidative stress and inflammatory process, through the regulation of the TLR4/Myd88/NF-kβ signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rivaroxaban Modulates TLR4/Myd88/NF-Kβ Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression

et al. 2021

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“…Due to the recent marketing authorization, molecular studies on the pharmacological actions of vortioxetine are limited until now. For example, Yu et al , Lu et al and Sun et al ., ( Yu et al, 2017 ; Lu et al, 2018 ; Sun et al, 2020 ) all reported that vortioxetine administration significantly increased the hippocampal brain-derived neurotrophic factor (BDNF) -cAMP-response element binding protein (CREB) signaling cascade in rodent models of depression. Du Jardin et al ., ( du Jardin et al, 2016 ) showed that a single dose of vortoxetine increased the expression of several plasticity-related genes (mTOR, Mglur1, Pkcα, Homer3, Spinophilin, and Synapsin3) in the rat frontal cortex.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal PPARα Plays a Role in the Pharmacological Mechanism of Vortioxetine, a Multimodal-Acting Antidepressant

Wang

Liu

et al. 2021

Front. Pharmacol.

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As a well-known multimodal-acting antidepressant, vortioxetine is thought to aim at several serotonin (5-HT) receptors and the 5-HT transporter. However, recently more and more proteins besides 5-HT are being reported to participate in the antidepressant mechanism of vortioxetine. As a widely known nuclear hormone receptor, peroxisome proliferator activated receptor α (PPARα) possesses transcriptional activity and is very important in the brain. Several reports have suggested that hippocampal PPARα is implicated in antidepressant responses. Here we speculate that hippocampal PPARα may participate in the antidepressant mechanism of vortioxetine. In this study, chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS), behavioral tests, the western blotting and adenovirus associated virus (AAV)-mediated gene knockdown methods were used together. It was found that vortioxetine administration significantly reversed the inhibitory actions of both CUMS and CSDS on the hippocampal PPARα expression. Pharmacological blockade of PPARα notably prevented the antidepressant actions of vortioxetine in the CUMS and CSDS models. Moreover, genetic knockdown of PPARα in the hippocampus also significantly blocked the protecting effects of vortioxetine against both CUMS and CSDS. Therefore, the antidepressant effects of vortioxetine in mice require hippocampal PPARα.

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“… 88 Moreover, VO increases the level of the BDNF, restoring lost neurons, and potentially contributes to recovery from chronic pain. 62 , 89 – 92 …”

Section: Mechanism Of Actionmentioning

confidence: 99%

Vortioxetine as a new frontier in the treatment of chronic neuropathic pain: a review and update

Adamo

Calabria

Coppola

et al. 2021

Therapeutic Advances in Psychopharmacology

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Chronic neuropathic pain (CNP) is a disabling medical condition that impairs the health-related quality-of-life of affected patients. A high prevalence of anxiety, depression, sleep disturbance and cognitive impairment has frequently been reported in association with CNP, making the management of this disease complex and often multidisciplinary. Dual-acting agents such as selective serotonin and noradrenalin reuptake inhibitors (SNRIs) are considered particularly useful in the modulation of pain and in treatment of the mood disorders frequently associated with CNP. Recent evidence suggests that the top-down inhibitory control of pain involves the engagement and enhancement of descending endogenous opioidergic, cannabinoid and serotonergic systems, with the effect of serotonin being particularly related to the receptor subtypes that are preferentially activated; indeed serotonin induces analgesia via activation of 5-HT7 receptors and hyperalgesia via activation of 5-HT3 receptors. Vortioxetine (VO) is a novel multimodal serotonergic antidepressant with a unique mechanism of action. It has been demonstrated recently in experimental and clinical studies to have efficacy on pain hypersensitivity and on mood disorders. This drug inhibits the serotonin transporter with a high affinity, antagonises the 5-HT3, 5-HT1D and 5HT7 serotonin receptors, and activates the 5-HT1A and 5-HT1B receptors. In clinical studies, VO has proved effective at a dose of 10–20 mg/daily in short- and long-term treatment of patients with chronic orofacial pain, demonstrating a higher rate of clinical response and remission, a better acceptability, safety rate and tolerability, and a lower latency of action compared with other antidepressants. In the light of these recent findings, VO may be considered as a new pharmacological treatment also in relation to various types of CNP, particularly in elderly patients with concomitant mood disorders and cognitive impairment. The purpose of this review is to provide an up-to-date overview of the pharmacology and clinical applications of VO and to highlight its potential therapeutic properties and advantages in the management of CNP.

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Effects of Vortioxetine on depression model rats and expression of BDNF and Trk B in hippocampus

Cited by 12 publications

References 31 publications

Rivaroxaban Modulates TLR4/Myd88/NF-Kβ Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression

Rivaroxaban Modulates TLR4/Myd88/NF-Kβ Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression

Hippocampal PPARα Plays a Role in the Pharmacological Mechanism of Vortioxetine, a Multimodal-Acting Antidepressant

Vortioxetine as a new frontier in the treatment of chronic neuropathic pain: a review and update

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