The rapid antidepressant effect of ketamine in rats is associated with down-regulation of pro-inflammatory cytokines in the hippocampus

Wang, Nan; Yu, Hua; Shen, Xiaofeng; Gao, Zhiqin; Yang, Chun; Yang, Jianjun; Zhang, Guang-Fen

doi:10.3109/03009734.2015.1060281

Cited by 81 publications

(59 citation statements)

References 45 publications

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“…Also, it has been reported that venlafaxine has an anti-inflammatory effect by the way of suppression on interferon-γ/IL-10 production ratio. The increased hippocampal levels of pro-inflammatory cytokines have been found in the CUMS model of depression, and the improvement of CUMS-induced depression-like behaviors are associated with a reduction of pro-inflammatory cytokines in the rat hippocampus [47, 48]. In addition, the astrocytes have been damaged and their immunoreactivity decrease in the hippocampus of rats exposed to the CUMS [28, 49].…”

Section: Discussionmentioning

confidence: 99%

Venlafaxine ameliorates the depression-like behaviors and hippocampal S100B expression in a rat depression model

Wang

Zhang

et al. 2016

Behav Brain Funct

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BackgroundAccumulating evidence has indicated that S100B may be involved in the pathophysiology of depression. No published study has examined the effect of the antidepressant drug venlafaxine on S100B in animal models of depression. This study investigated S100B expression in the hippocampus and assessed the effect of venlafaxine on S100B mRNA level and protein expression in rats exposed to chronic unpredictable mild stress (CUMS).MethodsForty Sprague-Dawley rats were randomly divided into four groups as control, 0, 5 and 10 mg venlafaxine groups. The venlafaxine groups were exposed to CUMS from day 2 to day 43. Venlafaxine 0, 5 and 10 mg/kg were then administered from day 23 to day 43. We performed behavioral assessments with weight change, open-field and sucrose preference, and analyzed S100B protein expression and mRNA level in the hippocampus.ResultsThe CUMS led to a decrease in body weight, locomotor activity and sucrose consumption, but venlafaxine treatment (10 mg) reversed these CUMS-induced decreases Also, CUMS increased S100B protein expression and mRNA level in the hippocampus, but venlafaxine treatment (10 mg) significantly decreased S100B protein expression and mRNA level, which were significantly lower than the other treatment groups, without significant difference between the 10 mg venlafaxine and the control groups.ConclusionsOur findings showed that venlafaxine treatment (10 mg) may improve the depression-like behaviors and decrease over-expression of S100B protein and mRNA in the hippocampus in a rat model of depression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12993-016-0116-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Venlafaxine ameliorates the depression-like behaviors and hippocampal S100B expression in a rat depression model

Wang

Zhang

et al. 2016

Behav Brain Funct

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“…Expression and regulation of the DOs indicate that enhanced DO activity and elevated DO expression are correlated with depression symptomology in both human and rodent models (Brooks et al, 2016b; Capuron et al, 2002; O’Connor et al, 2009a). In preclinical studies, neuroinflammation induced by LPS administration, polyinosinic:polycytidylic acid (pI:C) treatment, peritoneal infection with Mycobacterium bovis or acute/chronic stress culminate in depression-like behaviors such as anhedonia and helplessness/despair (Dantzer and Kelley, 2007; Dantzer et al, 2011; Gibney et al, 2013; Hoyo-Becerra et al, 2014; Liu et al, 2015; Moreau et al, 2008; Wang et al, 2015a). Such pre-clinical models of depression are associated with increased DO expression and/or DO activity, primarily attributed to Ido1 as diminishing DO activity by the administration of Ido1 inhibitors or using Ido1 knockout (KO) mice results in decreased inflammation- and stress-induced depression-like behaviors (Lawson et al, 2013; Liu et al, 2015; O’Connor et al, 2009b; Salazar et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Desipramine decreases expression of human and murine indoleamine-2,3-dioxygenases

Brooks

Janda

Lawson

et al. 2017

Brain, Behavior, and Immunity

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Abundant evidence connects depression symptomology with immune system activation, stress and subsequently elevated levels of kynurenine. Anti-depressants, such as the tricyclic norepinephrine/serotonin reuptake inhibitor desipramine (Desip), were developed under the premise that increasing extracellular neurotransmitter level was the sole mechanism by which they alleviate depressive symptomologies. However, evidence suggests that anti-depressants have additional actions that contribute to their therapeutic potential. The Kynurenine Pathway produces tryptophan metabolites that modulate neurotransmitter activity. This recognition identified another putative pathway for anti-depressant targeting. Considering a recognized role of the Kynurenine Pathway in depression, we investigated the potential for Desip to alter expression of rate-limiting enzymes of this pathway: indoleamine-2,3-dioxygenases (Ido1 and Ido2). Mice were administered lipopolysaccharide (LPS) or synthetic glucocorticoid dexamethasone (Dex) with Desip to determine if Desip alters indoleamine-dioxygenase (DO) expression in vivo following a modeled immune and stress response. This work was followed by treating murine and human peripheral blood mononuclear cells (PBMCs) with interferon-gamma (IFNγ) and Desip. In vivo: Desip blocked LPS-induced Ido1 expression in hippocampi, astrocytes, microglia and PBMCs and Ido2 expression by PBMCs. Ex vivo: Desip decreased IFNγ-induced Ido1 and Ido2 expression in murine PBMCs. This effect was directly translatable to the human system as Desip decreased IDO1 and IDO2 expression by human PBMCs. These data demonstrate for the first time that an anti-depressant alters expression of Ido1 and Ido2, identifying a possible new mechanism behind anti-depressant activity. Furthermore, we propose the assessment of PBMCs for anti-depressant responsiveness using IDO expression as a biomarker.

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“…As is well-known, the microglia plays a key role in inflammation response of CNS [13]. And several researches have reported that ketamine could inhibit inflammatory cytokine release in systemic inflammatory response syndrome [14,15]. Thus, we hypothesized that ketamine's antidepressant effects may be related to its anti-inflammation action in CNS.…”

Section: Discussionmentioning

confidence: 91%

The effect of ketamine on microglia and proinflammatory cytokines in the hippocampus of depression-like rat

Chen¹,

Feng²,

Liu³

et al. 2017

Neuropsychiatry

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Mounting evidence suggests that activation of microglia and inflammatory response play an important role in the pathogenesis of depression. A single or repeated sub-anesthetic dose of ketamine administration induced fast and potent antidepressant effect. We investigated the effect of ketamine on microglia activation and pro-inflammatory cytokines levels in hippocampus of depression-like rats. Methods Forty-eight rats were equally randomized into four groups Control+saline group, Control+ketamine group, Chronic unpredictable mild stress (CUMS)+saline group and CUMS+ketamine group. 0.9% saline or 10 mg/kg ketamine was given once daily for 7 consecutive days. The sucrose preference test (SPT) open field test (OFT) and forced swimming test (FST) were performed before and day 7 after drug treatment. The hippocampus was subsequently harvested for the detection of levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and levels of CD11b and Iba1. The CD11bpositive cells in the CA3 and DG region of the hippocampus were also stained by immunohistochemistry. Results CUMS induced the decrease of sucrose solution intake volume, the increase of the immobility time, the up-regulation of TNF-α, IL-1β, IL-6, CD11b and Iba1 levels of the hippocampus and the increase of CD11b-positive microglia in the CA3 and DG region of the hippocampus. Ketamine administration could reverse this effect. Conclusion Ketamine's antidepressant effect on depression-like rats is accompanied by the inhibition of microglia activation and pro-inflammatory cytokines levels in the hippocampus.

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The rapid antidepressant effect of ketamine in rats is associated with down-regulation of pro-inflammatory cytokines in the hippocampus

Cited by 81 publications

References 45 publications

Venlafaxine ameliorates the depression-like behaviors and hippocampal S100B expression in a rat depression model

Venlafaxine ameliorates the depression-like behaviors and hippocampal S100B expression in a rat depression model

Desipramine decreases expression of human and murine indoleamine-2,3-dioxygenases

The effect of ketamine on microglia and proinflammatory cytokines in the hippocampus of depression-like rat

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