Depressive-like behavior induced by tumor necrosis factor-α is abolished by agmatine administration

Neis, Vivian B.; Manosso, Luana M.; Moretti, Morgana; Freitas, Andiara E.; Daufenbach, Juliana F.; Rodrigues, Ana Lúcia S.

doi:10.1016/j.bbr.2013.12.038

Cited by 57 publications

(22 citation statements)

References 66 publications

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“…IL-18, MCP-1, TNF-α, and IFN-γ were increased relative to healthy controls. These data concur with other studies showing that, for example, intracerebroventricular administration of TNF-α induces depression and anxiety behavior in rats and mice (Connor, Song et al 1998, Kaster, Gadotti et al 2012, Neis, Manosso et al 2014), as well as reports demonstrating that anxiety in the open field test is highly suppressed in IL-18 knockout mice, compared to wild type mice (Yaguchi, Nagata et al 2010). In future studies, it will be important to examine other brain regions, such as the frontal cortex, for depression-induced inflammation.…”

Section: Discussionsupporting

confidence: 92%

Inflammation is increased with anxiety- and depression-like signs in a rat model of spinal cord injury

Maldonado‐Bouchard

Peters

Woller

et al. 2016

Brain, Behavior, and Immunity

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Spinal cord injury (SCI) leads to increased anxiety and depression in as many as 60% of patients. Yet, despite extensive clinical research focused on understanding the variables influencing psychological well-being following SCI, risk factors that decrease it remain unclear. We hypothesized that excitation of the immune system, inherent to SCI, may contribute to the decrease in psychological well-being. To test this hypothesis, we used a battery of established behavioral tests to assess depression and anxiety in spinally contused rats. The behavioral tests, and subsequent statistical analyses, revealed three cohorts of subjects that displayed behavioral characteristics of 1) depression, 2) depression and anxiety, or 3) no signs of decreased psychological well-being. Subsequent molecular analyses demonstrated that the psychological cohorts differed not only in behavioral symptoms, but also in peripheral (serum) and central (hippocampi and spinal cord) levels of pro-inflammatory cytokines. Subjects exhibiting a purely depression-like profile showed higher levels of pro-inflammatory cytokines peripherally, whereas subjects exhibiting a depression- and anxiety-like profile showed higher levels of pro-inflammatory cytokines centrally (hippocampi and spinal cord). These changes in inflammation were not associated with injury severity; suggesting that the association between inflammation and the expression of behaviors characteristic of decreased psychological well-being was not confounded by differential impairments in motor ability. These data support the hypothesis that inflammatory changes are associated with decreased psychological well-being following SCI.

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Section: Discussionsupporting

confidence: 92%

Inflammation is increased with anxiety- and depression-like signs in a rat model of spinal cord injury

Maldonado‐Bouchard

Peters

Woller

et al. 2016

Brain, Behavior, and Immunity

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“…Similar to the previous studies, one of the latest findings from another study reported that NLRP3 inflammasome was activated in the hippocampus of CUMS‐exposed rats . Furthermore, this effect was found along with increased hippocampal oxidative‐nitrosative markers, inflammatory cytokines and iNOS, which supports the notion of agmatine as an antidepressant molecule that competitively inhibits iNOS and has anti‐inflammatory and antioxidant properties due to the fact that it could suppress NLRP3 inflammasome activation and inflammatory processes in response to stress . Thus, in the present study, we found that acute agmatine treatment was able to inhibit NLRP3 inflammasome activation and reduce subsequent pro‐inflammatory cytokine levels not only in both brain regions, but also in the serum of stressed rats.…”

Section: Discussionsupporting

confidence: 91%

“…Up to the present, there are less but suggestive reports regarding agmatine's anti‐inflammatory effects . In a recent study, agmatine has been shown to reverse depressive‐like behaviours induced by TNF‐α administration in mice . However, there is still a lack of understanding regarding the molecular mechanisms that may at least partially contribute to the proposed immunomodulatory effects of agmatine in stress‐related conditions.…”

mentioning

confidence: 97%

Agmatine Reverses Sub‐chronic Stress induced Nod‐like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats

Şahin

Albayrak

Akdeniz

et al. 2016

Basic Clin Pharma Tox

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The activation of Nod-like receptor protein 3 (NLRP3) has lately been implicated in stress and depression as an initiator mechanism required for the production of interleukin (IL)-1b and IL-18. Agmatine, an endogenous polyamine widely distributed in mammalian brain, is a novel neurotransmitter/neuromodulator, with antistress, anxiolytic and antidepressant-like effects. In this study, we examined the effect of exogenously administered agmatine on NLRP3 inflammasome pathway/cytokine responses in rats exposed to restraint stress for 7 days. The rats were divided into three groups: stress, stress+agmatine (40 mg/kg; i.p.) and control groups. Agmatine significantly down-regulated the gene expressions of all stress-induced NLRP3 inflammasome components (NLRP3, NF-jB, PYCARD, caspase-1, IL-1b and IL-18) in the hippocampus and prefrontal cortex (PFC) and reduced pro-inflammatory cytokine levels not only in both brain regions, but also in serum. Stress-reduced levels of IL-4 and IL-10, two major anti-inflammatory cytokines, were restored back to normal by agmatine treatment in the PFC. The findings of the present study suggest that stress-activated NLRP3 inflammasome and cytokine responses are reversed by an acute administration of agmatine. Whether antidepressant-like effect of agmatine can somehow, at least partially, be mediated by the inhibition of NLRP3 inflammasome cascade and relevant inflammatory responses requires further studies in animal models of depression.

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“…In the central nervous system, agmatine binds 26 to various receptors and is considered a novel neurotransmitter [1,2]. This compound also 27 elicits antinociceptive, antidepressive and anxiolytic properties [3,4,5]. In the cardiovascular 28 system, recent studies indicated that agmatine can decrease heart rate and blood pressure [6,7], 29 and is therefore a potential treatment for cardiovascular diseases such as hypertension, ischemia, 30 diabetes, atherosclerosis and angiogenesis [8].…”

mentioning

confidence: 99%

Enzymatic production of agmatine by recombinant arginine decarboxylase

Sun

Song

Liu

2015

Journal of Molecular Catalysis B: Enzymatic

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Depressive-like behavior induced by tumor necrosis factor-α is abolished by agmatine administration

Cited by 57 publications

References 66 publications

Inflammation is increased with anxiety- and depression-like signs in a rat model of spinal cord injury

Inflammation is increased with anxiety- and depression-like signs in a rat model of spinal cord injury

Agmatine Reverses Sub‐chronic Stress induced Nod‐like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats

Enzymatic production of agmatine by recombinant arginine decarboxylase

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