NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings

Kaufmann, Fernanda Neutzling; Costa, Ana Paula; Ghisleni, Gabriele; Diaz, Alexandre Paim; Rodrigues, Ana Lúcia S.; Peluffo, Hugo; Kaster, Manuella P.

doi:10.1016/j.bbi.2017.03.002

Cited by 298 publications

(160 citation statements)

References 244 publications

Supporting

Mentioning

152

Contrasting

Unclassified

Order By: Relevance

“…Chronic treatment with the standard antidepressant drug fluoxetine suppressed all symptoms induced by UCMS in rodents (Pan et al, 2014;Du et al, 2016). There is a multitude of review articles available which give further insight to the causal relationship between inflammasome activation and MD (Alcocer-Gómez et al, 2016;Kaufmann et al, 2017;Franklin et al, 2018;Herman and Pasinetti, 2018).…”

Section: The P2x7r Triggers Neuroinflammation and Subsequent Mood Dismentioning

confidence: 99%

Pathological ATPergic Signaling in Major Depression and Bipolar Disorder

Illéš

Verkhratsky

Tang

2020

Front. Mol. Neurosci.

View full text Add to dashboard Cite

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.

show abstract

Section: The P2x7r Triggers Neuroinflammation and Subsequent Mood Dismentioning

confidence: 99%

Pathological ATPergic Signaling in Major Depression and Bipolar Disorder

Illéš

Verkhratsky

Tang

2020

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…NLRP3 inflammasome is involved in many innate immune processes related to infection, inflammation, and autoimmunity [8]. NLRP3 inflammasome is a bridge between immune activation and stress exposure; the latter promotes the development of depression through the activation of NLRP3 inflammasome [9,10]. e interleukin-1 beta (IL-1β) and IL-18 levels are increased in the peripheral blood monocytes of patients with major depression due to the activation of NLRP3 inflammasome [11].…”

Section: Introductionmentioning

confidence: 99%

trans-Cinnamaldehyde Reverses Depressive-Like Behaviors in Chronic Unpredictable Mild Stress Rats by Inhibiting NF-κB/NLRP3 Inflammasome Pathway

Wang

Zhou

et al. 2020

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

trans-Cinnamaldehyde (TCA) is the main active component extracted from Cinnamomum cassia (C. cassia), which has many pharmacological effects, such as anti-inflammation, lowering blood glucose, and improving nerve function. However, there is no report of TCA in the treatment of depression. e purpose of this study was to investigate the antidepressant-like effect of TCA and the mechanism of NF kappa B (NF-κB) pathway and NLRP3 inflammasome inhibition by TCA. We divided 40 rats into the control group, CUMS group, FLU group, and the TCA group. e activation of the NF-κB pathway and NLRP3 inflammasome in prefrontal cortex and hippocampus of rats in each group was observed. After the treatments with FLU and TCA, the sucrose consumptions in rats increased significantly and the immobility time in forced swimming was decreased significantly compared to the CUMS group. e expression of TLR4, NF-κB-1, p-p65, TNF-α, NLRP3, ASC, caspase-1, IL-1β, and IL-18 proteins in prefrontal cortex and hippocampus was decreased, and the expression of IL-1β, IL-18, and TNF-α in serum was downregulated compared to the CUMS group. Similar to FLU, TCA reverses the depression-like behaviors in rats, which indicates that TCA has a significant antidepressant-like effect. e mechanism of the antidepressant property of TCA might be that it inhibits the activation of the NF-κB pathway and NLRP3 inflammasome in the prefrontal cortex and hippocampus of CUMS rats.

show abstract

“…In the CNS, this so‐called ongoing inflammation occurring during pathogenesis of a variety of neurological disorders can be mediated via activation of the NLRP3 inflammasome, a key innate immune sensor for danger signals (Figures and ). The functions of the NLRP3 inflammasome in neuroinflammation have been implicated in progression of several neurological disorders, including AD, PD, TBI, stroke, depression, and MS …”

Section: Role Of Nlrp3 Inflammasome‐mediated Neuroinflammation In Neumentioning

confidence: 99%

Targeting the NLRP3 Inflammasome in Neuroinflammation: Health Promoting Effects of Dietary Phytochemicals in Neurological Disorders

Hung

Pan

2019

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Neurological disorders occur in the central and peripheral nervous system and include Alzheimer's disease, stroke, and spinal cord injury. Activation of the innate immune system inevitably occurs in all forms of neurological disorders. The NOD‐, LRR‐ and pyrin domain‐containing 3 (NLRP3) inflammasome is a multimolecular complex that can sense danger signals associated with neurological disorders. Assembly of the NLRP3 inflammasome promotes caspase‐1‐mediated interleukin‐1β and interleukin‐18 maturation in microglia, where neuroinflammation contributes to neurological disease development and progression. Thus, this review attempts to elucidate the current knowledge regarding NLRP3 inflammasome activation and its crucial role in the pathogenesis of neurological disorders. Recent scientific findings with respect to neuroprotective effects of dietary phytochemicals against NLRP3 inflammasome‐mediated neurological disorders summarized in this review suggest that modulation of the NLRP3 inflammasome assembly by plant‐derived phytochemicals could be a potential strategy for prevention or treatment of neurological disorders.

show abstract

NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings

Cited by 298 publications

References 244 publications

Pathological ATPergic Signaling in Major Depression and Bipolar Disorder

Pathological ATPergic Signaling in Major Depression and Bipolar Disorder

trans-Cinnamaldehyde Reverses Depressive-Like Behaviors in Chronic Unpredictable Mild Stress Rats by Inhibiting NF-κB/NLRP3 Inflammasome Pathway

Targeting the NLRP3 Inflammasome in Neuroinflammation: Health Promoting Effects of Dietary Phytochemicals in Neurological Disorders

Contact Info

Product

Resources

About