Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses
Open accessAbstract
Neuro-inflammation has been shown to play a critical role in the development of depression. Beta-hydroxybutyrate (BHB) is a ketone body and has recently been reported to exert anti-inflammatory effects via inhibition of NLRP3 inflammasome. Here, we investigated the potential antidepressant and anti-inflammatory effects of BHB on rats exposed to acute and chronic stress. We examined the influence of repeated BHB administration on depressive and anxiety behaviors in a rodent model of chronic unpredictable stress (CUS). Additionally, the influence of acute immobilization (IMM) stress and single BHB administration on hippocampal interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were assessed. Repeated administration of BHB attenuated CUS-induced depressive- and anxiety-related behaviors. IMM stress increased levels of IL-1β in the hippocampus, while a single pre-administration of BHB attenuated this increase. Although no effect was observed on hippocampal TNF-α levels after 1 h of IMM stress, a single BHB pre-administration reduced hippocampal TNF-α. Our previous report showed that the release of IL-1β and TNF-α caused by stress is tightly regulated by NLRP3 inflammasome. These findings demonstrate that BHB exerts antidepressant-like effects, possibly by inhibiting NLRP3-induced neuro-inflammation in the hippocampus, and that BHB may be a novel therapeutic candidate for the treatment of stress-related mood disorders.
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β-hydroxybutyrate exerts an antidepressant-like effect in a rodent model of chronic unpredictable stress.
“β-hydroxybutyrate exerts an antidepressant-like effect in a rodent model of chronic unpredictable stress189,190.”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [189]
BHB exerts antidepressant-like effects, possibly by anti-inflammatory mechanisms that inhibit or are led by NLRP3-induced neuroinflammation in the hippocampus.
“These findings suggest that BHB exerts antidepressant-like effects, possibly by anti-inflammatory mechanisms that inhibits or are led by NLRP3-induced neuro-inflammation in the hippocampus (255).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [255]
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- Authors
- Yamanashi, T., Iwata, M., Kamiya, N., Tsunetomi, K., Kajitani, N., Wada, N., Iitsuka, T., Yamauchi, T., Miura, A., Pu, S., Shirayama, Y., Watanabe, K., Duman, R. S., & Kaneko, K.
- Affiliations
- Tottori University (JP)
- Nara Medical University (JP)
- Teikyo University Chiba Medical Center (JP)
- Yale University (US)
- Corresponding author
- Iwata, Masaaki
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-08-09
- Volume
- 7
- Issue
- 1
- Pages
- 7677-7677
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5550422
- OpenAlex
- W2744221345
- Cited by
- 214
- References
- 46
- Citations by year
- 2026: 22 · 2025: 25 · 2024: 31 · 2023: 23 · 2022: 27 · 2021: 29 · 2020: 26 · 2019: 19 · 2018: 10 · 2017: 1
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Tottori University research result repository (Tottori University) (submittedVersion, cc-by)
- Funders
- Yale University
- Japan Society for the Promotion of Science (17K10273, 25861006)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- beta-hydroxybutyrate, NLRP3 inflammasome, neuroinflammation, depression, anxiety, chronic unpredictable mild stress, restraint stress, hippocampus, IL-1β, TNF-α, ketone bodies, antidepressant effects
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Anxiety, Behavior, Animal, Depression, Hippocampus, Inflammation, Male, Stress, Physiological, Stress, Psychological, Biomarkers, Cytokines, 3-Hydroxybutyric Acid, Rats
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