Cited by 214Tryptophan and brain disordersTreatment of Major DepressionStress Responses and Cortisol

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Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses

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Yamanashi, Takehiko, Iwata, Masaaki, Kamiya, Naho, Tsunetomi, Kyohei, Kajitani, Naofumi, Wada, Nodoka, Iitsuka, Takahiro, Yamauchi, Takahira, Miura, Akihiko, Pu, Shenghong, Shirayama, Yukihiko, Watanabe, Ken, Duman, Ronald S., Kaneko, Koichi·2017·Scientific Reports

DOI 10.1038/s41598-017-08055-1PMC PMC5550422

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Abstract

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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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: Yamanashi, Takehiko
Iwata, Masaaki
Yamauchi, Takahira
Shirayama, Yukihiko
Watanabe, Ken
Duman, Ronald S.
Venue: Scientific Reports
Publisher: Springer Science and Business Media LLC
Published: 2017-08-09
Volume: 7
Issue: 1
Pages: 7677-7677
ISSN: 2045-2322 (ISSN-L)
DOI: 10.1038/s41598-017-08055-1
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
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
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 (medical) › 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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Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses

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