Psychological Stress Activates the Inflammasome via Release of Adenosine Triphosphate and Stimulation of the Purinergic Type 2X7 Receptor

Iwata, Masaaki; Ota, Kristie T.; Li, Xiaoyuan; Sakaue, Fumika; Li, Nanxin; Dutheil, Sophie; Banasr, Mounira; Đurić, Vanja; Yamanashi, Takehiko; Kaneko, Koichi; Rasmussen, Kurt; Glasebrook, Andrew L.; Köester, Anja; Song, Dekun; Jones, Kenneth A.; Zorn, Stevin H.; Smagin, Gennady; Duman, Ronald S.

doi:10.1016/j.biopsych.2015.11.026

Cited by 323 publications

(321 citation statements)

References 64 publications

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“…A recent investigation by Iwata et al (2015) also found that 21 days of CUS resulted in a depressive behavioral phenotype including decreased sucrose preference, which was abrogated in NLRP3 KO mice. In wild-type mice, they also found that peripheral administration of an IL-1β-blocking antibody ameliorated the behavioral effects of CUS, including decrements in sucrose preference and immobility in the forced swim test.…”

Section: Animal Models Of Depression: Role Of Inflammasomesmentioning

confidence: 91%

“…These findings suggest that stress-induced activation of the NLRP3 inflammasome and subsequent maturation and release of IL-1β was necessary for the depressive-like behavioral effects of stress. Iwata et al (2015) also explored the role of ATP, a well-characterized activator of the NLRP3 inflammasome (Elliott and Sutterwala, 2015), in stress-induced activation of NLRP3, IL-1β release, and behavioral effects, which we address in further detail below. Clearly, the studies by Alcocer-Gomez et al (2015) and Iwata et al (2015) provide strong evidence for a casual role for the NLRP3 inflammasome in the effects of stress on depressivelike behavior.…”

Section: Animal Models Of Depression: Role Of Inflammasomesmentioning

confidence: 99%

“…Iwata et al (2015) have found that exposure to acute immobilization stress (60 min) resulted in the intrahippocampal release of ATP concomitant with IL-1β protein as well as NLRP3 inflammasome activation. These effects of stress were prevented in a Nlrp3 KO mouse and were blocked by peripheral administration of an antagonist to the P2X7 receptor, which mediates ATP activation of the NLRP3 inflammasome (Jin and Flavell, 2010), suggesting that stress-induced release of ATP mediates NLRP3 inflammasome activation and subsequent release of IL-1β.…”

Section: Atpmentioning

confidence: 99%

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Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders

Fleshner

Frank

Maier

2016

Neuropsychopharmacol

183

125

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Major depressive disorder (MDD) and other mood disorders remain difficult to effectively treat, and innovative interventions and therapeutic targets are needed. Psychological stressors and inappropriate inflammation increase the risk and severity of mood disorders; however, only recently have the importance of sterile inflammatory processes in this effect been revealed. This review will introduce the reader to pathogen vs sterile inflammation, inflammatory receptor-ligand interactions, microbialassociated molecular patterns (MAMPs), pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and the more recent discovery of the role of the inflammasome in peripheral and central nervous system cytokine/chemokine inflammatory responses. The review will focus on current preclinical and clinical evidence that sterile inflammation and inflammasome-dependent signaling may contribute to mood disorders. By understanding these inflammatory signaling processes, new approaches for quieting chronic or inappropriate inflammatory states may be revealed and this could serve as novel pharmacological targets for the treatment of mood disorders.

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Section: Animal Models Of Depression: Role Of Inflammasomesmentioning

confidence: 91%

Section: Animal Models Of Depression: Role Of Inflammasomesmentioning

confidence: 99%

Section: Atpmentioning

confidence: 99%

See 1 more Smart Citation

Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders

Fleshner

Frank

Maier

2016

Neuropsychopharmacol

183

125

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“…Numerous studies have revealed microglial activation and enhanced neuroinflammatory signaling in a variety of stress models (O'Connor, Johnson et al 2003, Nair and Bonneau 2006, Frank, Baratta et al 2007, Kopp, Wick et al 2013, Iwata, Ota et al 2015. Moreover, recent studies indicate that microglial activation and neuroinflammatory signaling occurs particularly within stress-reactive brain regions including the frontal cortex, hypothalamus, amygdala, and hippocampus (Wohleb, Hanke et al 2011, Hinwood, Morandini et al 2012.…”

Section: Rsd Activates Stress Circuitry Promotes Neuroinflammation mentioning

confidence: 95%

Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal

Weber

Godbout

Sheridan

2016

Neuropsychopharmacol

240

159

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Mounting evidence indicates that proinflammatory signaling in the brain affects mood, cognition, and behavior and is linked with the etiology of psychiatric disorders, including anxiety and depression. The purpose of this review is to focus on stress-induced bidirectional communication pathways between the central nervous system (CNS) and peripheral immune system that converge to promote a heightened neuroinflammatory environment. These communication pathways involve sympathetic outflow from the brain to the peripheral immune system that biases hematopoietic stem cells to differentiate into a glucocorticoid-resistant and primed myeloid lineage immune cell. In conjunction, microglia-dependent neuroinflammatory events promote myeloid cell trafficking to the brain that reinforces stress-related behavior, and is argued to play a role in stress-related psychiatric disorders. We will discuss evidence implicating a key role for endothelial cells that comprise the blood-brain barrier in propagating peripheral-to-central immune communication. We will also discuss novel neuron-to-glia communication pathways involving endogenous danger signals that have recently been argued to facilitate neuroinflammation under various conditions, including stress. These findings help elucidate the complex communication that occurs in response to stress and highlight novel therapeutic targets against the development of stress-related psychiatric disorders.

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“…Besides CCL2, P2X7R activation also promotes IL-1β release and inflammasome activation to trigger depression-like behavior (Fig. 3) [244]. …”

Section: Neuroimmune Basis Of the Mechanisms Of Depressionmentioning

confidence: 99%

Neuroimmune and Inflammatory Signals in Complex Disorders of the Central Nervous System

Liberman

Trías

Chagas

et al. 2018

Neuroimmunomodulation

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An extensive microglial-astrocyte-monocyte-neuronal cross talk seems to be crucial for normal brain function, development, and recovery. However, under certain conditions neuroinflammatory interactions between brain cells and neuroimmune cells influence disease outcome and brain pathology. Microglial cells express a range of functional states with dynamically pleomorphic profiles from a surveilling status of synaptic transmission to an active player in major events of development such as synaptic elimination, regeneration, and repair. Also, inflammation mediates a series of neurotoxic roles in neuropsychiatric conditions and neurodegenerative diseases. The present review discusses data on the involvement of neuroinflammatory conditions that alter neuroimmune interactions in four different pathologies. In the first section of this review, we discuss the ability of the early developing brain to respond to a focal lesion with a rapid compensatory plasticity of intact axons and the role of microglial activation and proinflammatory cytokines in brain repair. In the second section, we present data of neuroinflammation and neurodegenerative disorders and discuss the role of reactive astrocytes in motor neuron toxicity and the progression of amyotrophic lateral sclerosis. In the third section, we discuss major depressive disorders as the consequence of dysfunctional interactions between neural and immune signals that result in increased peripheral immune responses and increase proinflammatory cytokines. In the last section, we discuss autism spectrum disorders and altered brain circuitries that emerge from abnormal long-term responses of innate inflammatory cytokines and microglial phenotypic dysfunctions.

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Psychological Stress Activates the Inflammasome via Release of Adenosine Triphosphate and Stimulation of the Purinergic Type 2X7 Receptor

Cited by 323 publications

References 64 publications

Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders

Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders

Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal

Neuroimmune and Inflammatory Signals in Complex Disorders of the Central Nervous System

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