Stress-Induced Depressive Behaviors Require a Functional NLRP3 Inflammasome
Abstract
Depression is a major public health concern in modern society, yet little is known about the molecular link between this condition and neuroinflammation. The inflammasome complex was recently shown to be implicated in depression. The present study shows the implication of NLRP3 inflammasome in animal model of stress-induced depression. Accordingly, we show here that in the absence of a NLRP3 inflammasome, prolonged stress does not provoke depressive behaviors or microglial activation in mice or dampen hippocampal neurogenesis. Indeed, NLRP3 deletion or inhibition of microglial activation impairs the stress-induced alterations associated with depression. According to these findings in animal model, the inflammasome could be a target for new therapeutic interventions to prevent depression in patients.
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In a small cohort of MDD patients, NLRP3 mRNA and protein levels are increased in PBMCs, as are caspase-1 and IL-1β, and normalize to healthy levels upon antidepressant treatment.
“A study involving a relatively small cohort of MDD patients and healthy volunteers reported that NLRP3 mRNA and protein levels are increased in peripheral blood mononuclear cells in MDD patients, as caspase-1 and IL-1β, and normalized to healthy levels upon antidepressant treatment (245).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [245]
Increased expression and activity of NLRP3 inflammasome machinery in circulating immune cells have been reported in patients with depression, bipolar disorder, and ASD.
“Increased expression and activity of the NLRP3 inflammasome machinery in circulating immune cells of patients affected by depression (245), bipolar disorder (246), and ASD (226), have been reported.”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [245]
A functional NLRP3 inflammasome appears necessary for the development of depressive behaviors induced by stress, since genetic depletion of NLRP3 in mice prevented stress-induced alterations associated with depression.
“A functional inflammasome NLRP3 appears to be necessary for the development of depressive behaviors induced by stress, since genetic depletion of NLRP3 in mice prevented the stress-induced alterations associated with depression, like decreased sucrose preference, reduced social interaction ratio and high immobility time in the FST [150].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [150]
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Self-citation
- Authors
- Alcocer-Gómez, E., Ulecia-Morón, C., Marín-Aguilar, F., Rybkina, T., Casas-Barquero, N., Ruiz-Cabello, J., Ryffel, B., Apetoh, L., Ghiringhelli, F., Bullón, P., Sánchez-Alcazar, J. A., Carrión, A. M., & Cordero, M. D.
- Affiliations
- Universidad Pablo de Olavide (ES)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Universidad de Sevilla (ES)
- Instituto de Biomedicina de Sevilla (ES)
- Corresponding author
- Cordero, Mario D.
- Venue
- Molecular Neurobiology
- Published
- 2015-09-11
- Volume
- 53
- Issue
- 7
- Pages
- 4874-4882
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W1906422585
- Cited by
- 172
- References
- 27
- Citations by year
- 2026: 5 · 2025: 17 · 2024: 13 · 2023: 20 · 2022: 17 · 2021: 25 · 2020: 20 · 2019: 17 · 2018: 9 · 2017: 13 · 2016: 16
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- NLRP3 inflammasome, depression, chronic stress, neuroinflammation, microglial activation, hippocampal neurogenesis, inflammasome inhibition, animal models of depression, therapeutic target
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Depression, Hippocampus, Interpersonal Relations, Male, Mice, Inbred C57BL, Stress, Psychological, Prefrontal Cortex, Microglia, Mice, Knockout, Mice, Inflammasomes
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