Involvement of inflammasome activation in lipopolysaccharide-induced mice depressive-like behaviors
Open accessAbstract
AIMS: The NLRP3 inflammasome is a cytoplasmic multiprotein complex of the innate immune system that regulates the cleavage of interleukin-1β and interleukin-18 precursors. It can detect a wide range of danger signals and trigger a series of immune-inflammatory reactions. There were plenty of studies indicating that activation of the immune system played pivotal roles in depression. However, the underlying mechanisms of immune-depression interactions remained elusive and there was no report about the involvement of inflammasome activation in depression. METHODS: We established an acute depression mouse model with lipopolysaccharide to explore the involvement of inflammasome activation in depression. RESULTS: The lipopolysaccharide-treated mice displayed depressive-like behaviors and pro-inflammatory cytokine interleukin-1β protein and mRNA levels significantly increased. The NLRP3 inflammasome mRNA expression level also significantly elevated in depressed mice brain. Pretreatment with the NLRP3 inflammasome inhibitor Ac-YVAD-CMK significantly abrogated the depressive-like behaviors induced by lipopolysaccharide. CONCLUSION: These data suggest for the first time that the NLRP3 inflammasome is involved in lipopolysaccharide-induced mice depressive-like behaviors. The NLRP3 inflammasome may be a central mediator between immune activation and depression, which raises the possibility that it may be a more specific target for the depression treatments in the near future.
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Selective inhibition of the NLRP3 inflammasome with systemic treatment using Ac-YVAD-CMK exhibited anti-inflammatory and antidepressant effects.
“selective inhibition of the NLRP3 inflammasome with systemic treatment using Ac-YVAD-CMK, exhibited anti-inflammatory and antidepressant effects [157,158]”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [158]
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- Authors
- Zhang, Y., Liu, L., Peng, Y., Liu, Y., Wu, T., Shen, X., Zhou, J., Sun, D., Huang, A., Wang, X., Wang, Y., & Jiang, C.
- Affiliations
- Second Military Medical University (CN)
- Laboratory of Stress Medicine Faculty of Psychology and Mental Health Second Military Medical University Shanghai China
- Department of Neurobiology Second Military Medical University Shanghai China
- Corresponding author
- Jiang, Chun‐Lei
- Venue
- CNS Neuroscience & Therapeutics
- Publisher
- Wiley
- Published
- 2013-11-27
- Volume
- 20
- Issue
- 2
- Pages
- 119-124
- ISSN
- 1755-5930 (ISSN-L)
- 1755-5949
- PMC
- PMC6493120
- OpenAlex
- W2061295164
- Cited by
- 200
- References
- 38
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 15 · 2023: 21 · 2022: 21 · 2021: 20 · 2020: 23 · 2019: 14 · 2018: 13 · 2017: 21 · 2016: 12 · 2015: 13 · 2014: 7
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- CNS Neuroscience & Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31371200, 81171124)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- NLRP3 inflammasome, depression, lipopolysaccharide, depression-like behavior, IL-1β, inflammatory cytokines, Ac-YVAD-cmk, innate immunity, neuroinflammation
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Amino Acid Chloromethyl Ketones, Animals, Brain, Carrier Proteins, Depression, Disease Models, Animal, Drug Administration Schedule, Food Preferences, Gene Expression Regulation, Inflammation, Lipopolysaccharides, Male, Mice, Inbred BALB C, RNA, Messenger, Sucrose, Swimming, Cysteine Proteinase Inhibitors, Caspase 1, Mice, Interleukin-1beta
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