Antidepressant-like effects of agmatine and NOS inhibitors in chronic unpredictable mild stress model of depression in rats: The involvement of NLRP inflammasomes

Özkartal, Ceren Şahin; Tüzün, Erdem; Küçükali, Cem İ̇smail; Ulusoy, Canan; Giriş, Murat; Arıcıoğlu, Feyza

doi:10.1016/j.brainres.2019.146438

Cited by 20 publications

(12 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is also worth quoting a recent study conducted by Ozkartal et al (73) that highlighted the role of nitric oxide synthase (NOS) in the activation of NLRP3 inflammasome; in this study, the administration of NOS inhibitors in chronically stressed mice prevented the activation of NLRP3 inflammasome and the production of IL-1β.…”

Section: Curcumin and Inflammasome Activationmentioning

confidence: 90%

“…In some other studies, suicidal and depressed patients had elevated levels of plasma NO and its metabolites (81,82). The overactivation of NOS pathway and subsequently increased nitric oxide has been described as an important pathophysiological factor in neuroinflammation and neurotoxicity processes involved in stress and depression (79,83) as well as an important modulating factor in the production of neurotransmitters such as noradrenaline, serotonin, and dopamine (79), thus explaining why NOS inhibitors can exert antidepressant and anxiolytic-like effects (73,84).…”

Section: Curcumin and Inflammasome Activationmentioning

confidence: 99%

“…There have been a few studies highlighting the role of NLRP3 inflammasome in depression. Animal studies investigating this theory showed that chronic stress could stimulate NLRP3 activation in rodent brains and that, accordingly, in the absence of the NLRP3 inflammasome activation, stress did not produce a depressive behavior, anhedonia, or social impairment in those mice (70)(71)(72)(73). It has also been shown that NLRP3 is activated in mononuclear cells in patients with depressive disorder and that some antidepressants compounds seem to show a decrease in NLRP3 activation (74).…”

Section: Curcumin and Inflammasome Activationmentioning

confidence: 99%

See 2 more Smart Citations

Curcumin in Depression: Potential Mechanisms of Action and Current Evidence—A Narrative Review

2020

View full text Add to dashboard Cite

Major depressive disorder (MDD) is one of the most prevalent and debilitating disorders. Current available treatments are somehow limited, so alternative therapeutic approaches targeting different biological pathways are being investigated to improve treatment outcomes. Curcumin is the main active component in the spice turmeric that has been used for centuries in Ayurvedic medicine to treat a variety of conditions, including anxiety and depressive disorders. In the past decades, curcumin has drawn researchers' attention and displays a broad range of properties that seem relevant to depression pathophysiology. In this review, we break down the potential mechanisms of action of curcumin with emphasis on the diverse systems that can be disrupted in MDD. Curcumin has displayed, in a number of studies, a potency in modulating neurotransmitter concentrations, inflammatory pathways, excitotoxicity, neuroplasticity, hypothalamic–pituitary–adrenal disturbances, insulin resistance, oxidative and nitrosative stress, and endocannabinoid system, all of which can be involved in MDD pathophysiology. To date, a handful of clinical trials have been published and suggest a benefit of curcumin in MDD. With evidence that is progressively growing, curcumin appears as a promising alternative option in the management of MDD.

show abstract

Section: Curcumin and Inflammasome Activationmentioning

confidence: 90%

Section: Curcumin and Inflammasome Activationmentioning

confidence: 99%

Section: Curcumin and Inflammasome Activationmentioning

confidence: 99%

See 1 more Smart Citation

Curcumin in Depression: Potential Mechanisms of Action and Current Evidence—A Narrative Review

2020

View full text Add to dashboard Cite

show abstract

“…Unlike NLRP3, NLRP1 is mainly presented in neurons and dominantly implicated in neuronal injury pathologies and cognitive impairment [28,32,33], which is a core feature of subjects with depression. Also, recent studies showed that chronic unpredictable mild stress (CUMS) increase the expression of NLRP1 inflammasome complexes in animal models [34,35]. However, the definitive role of NLRP1 inflammasome in depression remains unclear.…”

Section: Introductionmentioning

confidence: 99%

NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice

Song

Gao

Fan

et al. 2020

J Neuroinflammation

134

View full text Add to dashboard Cite

Background Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, and inflammation has been considered crucial components of the pathogenesis of depression. NLRP1 inflammasome-driven inflammatory response is believed to participate in many neurological disorders. However, it is unclear whether NLRP1 inflammasome is implicated in the development of depression. Methods Animal models of depression were established by four different chronic stress stimuli including chronic unpredictable mild stress (CUMS), chronic restrain stress (CRS), chronic social defeat stress (CSDS), and repeat social defeat stress (RSDS). Depressive-like behaviors were determined by sucrose preference test (SPT), forced swim test (FST), tail-suspension test (TST), open-field test (OFT), social interaction test (SIT), and light-dark test (LDT). The expression of NLRP1 inflammasome complexes, BDNF, and CXCL1/CXCR2 were tested by western blot and quantitative real-time PCR. The levels of inflammatory cytokines were tested by enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. Results Chronic stress stimuli activated hippocampal NLRP1 inflammasome and promoted the release of pro-inflammatory cytokines IL-1β, IL-18, IL-6, and TNF-α in mice. Hippocampal Nlrp1a knockdown prevented NLRP1 inflammasome-driven inflammatory response and ameliorated stress-induced depressive-like behaviors. Also, chronic stress stimuli caused the increase in hippocampal CXCL1/CXCR2 expression and low BDNF levels in mice. Interestingly, Nlrp1a knockdown inhibited the up-regulation of CXCL1/CXCR2 expression and restored BDNF levels in the hippocampus. Conclusions NLRP1 inflammasome-driven inflammatory response contributes to chronic stress induced depressive-like behaviors and the mechanism may be related to CXCL1/CXCR2/BDNF signaling pathway. Thus, NLRP1 inflammasome could become a potential antidepressant target.

show abstract

“…Since then, other studies have confirmed the antidepressant efficacy of agmatine in behavioral tests in rodents[ 39 - 41 ]. Subsequent studies implicated several molecular targets in the antidepressant effect of agmatine, namely the modulation of: (1) K + channels[ 42 ]; (2) NO synthesis[ 43 , 44 ]; and (3) several neurotransmitter receptors including NMDA receptors[ 38 , 45 ], AMPA receptors[ 46 , 47 ], GABA receptors[ 48 ], serotonin receptors[ 49 , 50 ], and opioid system receptors[ 51 ].…”

Section: Agmatine As a Novel Candidate For Fast Antidepressant Responsesmentioning

confidence: 99%

Agmatine as a novel candidate for rapid-onset antidepressant response

Valverde¹,

Camargo²,

Rodrigues³

2021

WJP

View full text Add to dashboard Cite

Major depressive disorder (MDD) is a disabling and highly prevalent mood disorder as well as a common cause of suicide. Chronic stress, inflammation, and intestinal dysbiosis have all been shown to play crucial roles in the pathophysiology of MDD. Although conventional antidepressants are widely used in the clinic, they can take weeks to months to produce therapeutic effects. The discovery that ketamine promotes fast and sustaining antidepressant responses is one of the most important breakthroughs in the pharmacotherapy of MDD. However, the adverse psychomimetic/dissociative and neurotoxic effects of ketamine discourage its chronic use. Therefore, agmatine, an endogenous glutamatergic modulator, has been postulated to elicit fast behavioral and synaptogenic effects by stimulating the mechanistic target of rapamycin complex 1 signaling pathway, similar to ketamine. However, recent evidence has demonstrated that the modulation of the NLR family pyrin domain containing 3 inflammasome and gut microbiota, which have been shown to play a crucial role in the pathophysiology of MDD, may also participate in the antidepressant-like effects of both ketamine and agmatine. This review seeks to provide evidence about the mechanisms that may underlie the fast antidepressant-like responses of agmatine in preclinical studies. Considering the anti-inflammatory properties of agmatine, it may also be further investigated as a useful compound for the management of MDD associated with a pro-inflammatory state. Moreover, the fast antidepressant-like response of agmatine noted in animal models should be investigated in clinical studies.

show abstract

Antidepressant-like effects of agmatine and NOS inhibitors in chronic unpredictable mild stress model of depression in rats: The involvement of NLRP inflammasomes

Cited by 20 publications

References 87 publications

Curcumin in Depression: Potential Mechanisms of Action and Current Evidence—A Narrative Review

Curcumin in Depression: Potential Mechanisms of Action and Current Evidence—A Narrative Review

NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice

Agmatine as a novel candidate for rapid-onset antidepressant response

Contact Info

Product

Resources

About