Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses
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...
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Nature Portfolio
2017
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oai:doaj.org-article:7a47716c1b5542f2802d09eae4f2cab72021-12-02T16:07:00ZBeta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses10.1038/s41598-017-08055-12045-2322https://doaj.org/article/7a47716c1b5542f2802d09eae4f2cab72017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08055-1https://doaj.org/toc/2045-2322Abstract 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.Takehiko YamanashiMasaaki IwataNaho KamiyaKyohei TsunetomiNaofumi KajitaniNodoka WadaTakahiro IitsukaTakahira YamauchiAkihiko MiuraShenghong PuYukihiko ShirayamaKen WatanabeRonald S. DumanKoichi KanekoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Medicine R Science Q |
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Medicine R Science Q Takehiko Yamanashi Masaaki Iwata Naho Kamiya Kyohei Tsunetomi Naofumi Kajitani Nodoka Wada Takahiro Iitsuka Takahira Yamauchi Akihiko Miura Shenghong Pu Yukihiko Shirayama Ken Watanabe Ronald S. Duman Koichi Kaneko Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses |
| description |
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. |
| format |
article |
| author |
Takehiko Yamanashi Masaaki Iwata Naho Kamiya Kyohei Tsunetomi Naofumi Kajitani Nodoka Wada Takahiro Iitsuka Takahira Yamauchi Akihiko Miura Shenghong Pu Yukihiko Shirayama Ken Watanabe Ronald S. Duman Koichi Kaneko |
| author_facet |
Takehiko Yamanashi Masaaki Iwata Naho Kamiya Kyohei Tsunetomi Naofumi Kajitani Nodoka Wada Takahiro Iitsuka Takahira Yamauchi Akihiko Miura Shenghong Pu Yukihiko Shirayama Ken Watanabe Ronald S. Duman Koichi Kaneko |
| author_sort |
Takehiko Yamanashi |
| title |
Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses |
| title_short |
Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses |
| title_full |
Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses |
| title_fullStr |
Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses |
| title_full_unstemmed |
Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses |
| title_sort |
beta-hydroxybutyrate, an endogenic nlrp3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/7a47716c1b5542f2802d09eae4f2cab7 |
| work_keys_str_mv |
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1718384784745431040 |