Ketamine Alleviates Depressive-Like Behaviors &lt;i&gt;via&lt;/i&gt; Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice

Tan, Sisi; Wang, Yan; Chen, Ke; Zhang, Long; Zou, Jiong

doi:10.1248/bpb.b17-00131

Cited by 125 publications

(68 citation statements)

References 43 publications

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“…Since neuroinflammation plays a causative role in the pathophysiology of depression, targeting this pathway may hold promise for targeted therapy. Furthermore, several studies have proven that acute or chronic RS up-regulates pro-inflammatory cytokines associated with the development of depressive-like behaviors (56,57). Similarly, we found that RS led to the up-regulation of NF-κB, TNF-α, and IL-6 protein expressions in the PFC and HIP subregions.…”

Section: Discussionsupporting

confidence: 77%

Antidepressant and Anxiolytic Effect of Echium amoenum in Restraint Stress Model: The Role of Neuroinflammation in the Prefrontal Cortex and Hippocampus

Nouri

Farajdokht

Torbati

et al. 2019

Iran Red Crescent Med J

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Background: Echium amoenum (E. amoenum) is an Iranian medicinal plant with mood-enhancing effects. Objectives: This study was designed to investigate the effect of standardized E. amoenum hydroalcoholic extract on restraint stress (RS)-evoked anxiety-and-depressive-like behaviors in mice. Methods: This experimental study was conducted at the Tabriz University of Medical Sciences, Tabriz, Iran, in 2018. Doses of the hydroalcoholic extract of E. amoenum were optimized for rosmarinic acid (> %2 w/w) concentration of the extract. Other phytochemical indices, including total phenolic and flavonoid contents and radical scavenging activity, were also measured. For behavioral studies, 65 mice were randomly assigned into five groups (n = 13) of control, RS, RS + E75, RS + E150, and RS + E300. Animals in the RS group were subjected to the RS (3 h/day for 14 days) and treated with normal saline, while treatment groups received E. amoenum extract (75, 150, and 300 mg/kg, p.o.) concomitantly with RS exposure. Anxiety-like behaviors were assessed by Elevated Plus Maze (EPM) and Open Field Test (OFT). Depression was assessed by the forced swim test (FST) and Tail Suspension Test (TST). Western blotting was performed to determine the protein levels of IL-1β, NF-κB, TNF-α, and IL-6 in the prefrontal cortex (PFC) and hippocampus (HIP). The concentrations of corticosterone, alanine aminotransferase, aspartate aminotransferase, and alanine phosphatase were also measured in serum. Results: Moderate and high doses of the extract ameliorated RS-induced anxiety-(P < 0.05 in OFT and EPM) and depressive-like (P < 0.05 and P < 0.01 in FST; P < 0.01 and P < 0.001 in TST) behaviors. These results were approved by decreased serum corticosterone levels (P < 0.05 and P < 0.001). Furthermore, E. amoenum reduced the protein expression of neuroinflammatory markers in the HIP and PFC subregions (significant at least at P < 0.05 for IL-1β, NF-κB, and TNF-α). Although RS slightly increased the serum levels of liver enzymes, no histopathological changes were seen in the liver of the RS or E. amoenum-treated groups. Conclusions: E. amoenum can be an effective and safe complementary strategy for the treatment of stress-associated inflammation and behavioral changes.

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Section: Discussionsupporting

confidence: 77%

Antidepressant and Anxiolytic Effect of Echium amoenum in Restraint Stress Model: The Role of Neuroinflammation in the Prefrontal Cortex and Hippocampus

Nouri

Farajdokht

Torbati

et al. 2019

Iran Red Crescent Med J

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“…The role of P2X7Rs as essential activators of NLRP3 was also convincingly demonstrated by showing that UCMS elevates hippocampal P2X7R levels (Tan et al, 2017). The selective P2X7R antagonist Brilliant Blue G (BBG) attenuated the increase of immobility time in TST and FST in mice after activation of the inflammasome by LPS (Ma et al, 2014).…”

Section: The P2x7r Triggers Neuroinflammation and Subsequent Mood Dismentioning

confidence: 91%

Pathological ATPergic Signaling in Major Depression and Bipolar Disorder

Illéš

Verkhratsky

Tang

2020

Front. Mol. Neurosci.

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The mood disorders, major depression (MD) and bipolar disorder (BD), have a high lifetime prevalence in the human population and accordingly generate huge costs for health care. Efficient, rapidly acting, and side-effect-free pharmaceuticals are hitherto not available, and therefore, the identification of new therapeutic targets is an imperative task for (pre)clinical research. Such a target may be the purinergic P2X7 receptor (P2X7R), which is localized in the central nervous system (CNS) at microglial and neuroglial cells mediating neuroinflammation. MD and BD are due to neuroinflammation caused in the first line by the release of the pro-inflammatory cytokine interleukin-1β (IL-1β) from the microglia. IL-1β in turn induces the secretion of corticotropin-releasing hormone (CRH) and in consequence the secretion of adrenocorticotropic hormone (ACTH) and cortisol, which together with a plethora of further cytokines/chemokines lead to mood disorders. A number of biochemical/molecular biological measurements including the use of P2X7R-or IL-1β-deficient mice confirmed this chain of events. More recent studies showed that a decrease in the astrocytic release of ATP in the prefrontal cortex and hippocampus is a major cause of mood disorders. It is an attractive hypothesis that compensatory increases in P2X7Rs in these areas of the brain are the immediate actuators of MD and BD. Hence, blood-brain barrier-permeable P2X7R antagonists may be promising therapeutic tools to improve depressive disorders in humans.

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“…Chronic inflammatory reactions cause neurons apoptosis in brain regions associated with emotion regulation such as hippocampus, 132,133 leading to impairment of synaptic plasticity. Ketamine could normalize abnormal neurobehaviours induced by neuroinflammation through regulating the interleukin (IL)‐1β, tumour necrosis factor (TNF)‐α and IL‐6 134 . In rodent model, ketamine would reverse the increase in IL‐1β and TNF‐α caused by lipopolysaccharide (LPS), shortening the immobility time significantly in FST and promoting hippocampal neurogenesis 135 .…”

Section: Synaptic Plasticitymentioning

confidence: 99%

Rapid anti‐depressant‐like effects of ketamine and other candidates: Molecular and cellular mechanisms

Peng

Fan

et al. 2020

Cell Proliferation

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Major depressive disorder takes at least 3 weeks for clinical anti-depressants, such as serotonin selective reuptake inhibitors, to take effect, and only one-third of patients remit. Ketamine, a kind of anaesthetic, can alleviate symptoms of major depressive disorder patients in a short time and is reported to be effective to treatment-resistant depression patients. The rapid and strong anti-depressant-like effects of ketamine cause wide concern. In addition to ketamine, caloric restriction and sleep deprivation also elicit similar rapid anti-depressant-like effects. However, mechanisms about the rapid anti-depressant-like effects remain unclear. Elucidating the mechanisms of rapid anti-depressant effects is the key to finding new therapeutic targets and developing therapeutic patterns. Therefore, in this review we summarize potential molecular and cellular mechanisms of rapid anti-depressant-like effects based on the pre-clinical and clinical evidence, trying to provide new insight into future therapy.

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Ketamine Alleviates Depressive-Like Behaviors <i>via</i> Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice

Cited by 125 publications

References 43 publications

Antidepressant and Anxiolytic Effect of Echium amoenum in Restraint Stress Model: The Role of Neuroinflammation in the Prefrontal Cortex and Hippocampus

Antidepressant and Anxiolytic Effect of Echium amoenum in Restraint Stress Model: The Role of Neuroinflammation in the Prefrontal Cortex and Hippocampus

Pathological ATPergic Signaling in Major Depression and Bipolar Disorder

Rapid anti‐depressant‐like effects of ketamine and other candidates: Molecular and cellular mechanisms

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