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

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-...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5550422/
https://www.ncbi.nlm.nih.gov/pubmed/28794421
http://dx.doi.org/10.1038/s41598-017-08055-1
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author 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
author_facet 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
author_sort Yamanashi, Takehiko
collection PubMed
description 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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spelling pubmed-55504222017-08-11 Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses 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 Sci Rep Article 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. Nature Publishing Group UK 2017-08-09 /pmc/articles/PMC5550422/ /pubmed/28794421 http://dx.doi.org/10.1038/s41598-017-08055-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5550422/
https://www.ncbi.nlm.nih.gov/pubmed/28794421
http://dx.doi.org/10.1038/s41598-017-08055-1
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