Stress increases blood beta-hydroxybutyrate levels and prefrontal cortex NLRP3 activity jointly in a rodent model

Tsuyoshi Nishiguchi; Masaaki Iwata; Naofumi Kajitani; Akihiko Miura; Ryoichi Matsuo; Shumei Murakami; Yumeto Nakada; Shenghong Pu; Yuki Shimizu; Tatsuya Tsubakino; Takehiko Yamanashi; Gen Shinozaki; Jun Tsubota; Yukihiko Shirayama; Ken Watanabe; Koichi Kaneko

doi:10.1002/npr2.12164

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Stress increases blood beta-hydroxybutyrate levels and prefrontal cortex NLRP3 activity jointly in a rodent model

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Stress increases blood beta-hydroxybutyrate levels and prefrontal cortex NLRP3 activity jointly in a rodent model

Tsuyoshi Nishiguchi, Masaaki Iwata, Naofumi Kajitani, Akihiko Miura, Ryoichi Matsuo, Shumei Murakami, Yumeto Nakada, Shenghong Pu, Yuki Shimizu, Tatsuya Tsubakino, …

Neuropsychopharmacology reports, Vol.41(2), pp.159-167

02/20/2021

DOI: 10.1002/npr2.12164

PMCID: PMC8340844

PMID: 33609086

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Abstract

This study aimed to assess the response of endogenous beta-hydroxybutyrate to psychological stress, and its association with nucleotide-binding domain, leucine-rich repeat, pyrin domain-containing 3 (NLRP3) inflammasome, and stress-induced behavior. Male C57BL/6J mice were subjected to 1-hour restraint stress to examine changes in the endogenous beta-hydroxybutyrate and active NLRP3 levels in the prefrontal cortex. Subsequently, we created a depression model applying 10-day social defeat stress to the male C57BL/6J mice. One-hour restraint stress rapidly increased beta-hydroxybutyrate levels in the blood. The active NLRP3 levels in the prefrontal cortex also increased significantly. A correlation was found between the increased beta-hydroxybutyrate levels in the blood and the active NLRP3 levels in the prefrontal cortex. The mice exposed to social defeat stress exhibited depression- and anxiety-like behavioral changes in the open field, social interaction, and forced swim tests. There was a correlation between these behavioral changes and endogenous beta-hydroxybutyrate levels. Among the social defeat model mice, those with high beta-hydroxybutyrate levels tended to have more depression- and anxiety-like behavior. The increased blood beta-hydroxybutyrate levels due to psychological stress correlate with the active NLRP3 levels in the prefrontal cortex, suggesting that the increased beta-hydroxybutyrate levels due to stress may reflect a reaction to brain inflammation. In addition, mice with higher blood beta-hydroxybutyrate levels tend to exhibit increased depression- and anxiety-like behaviors; thus, an increase in blood beta-hydroxybutyrate levels due to stress may indicate stress vulnerability.

Stress

pyrin domain-containing 3 (NLRP3)

beta-hydroxybutyrate (BHB)

inflammasomes

leucine-rich repeat

prefrontal cortex

depression

nucleotide-binding domain

Details

Title: Subtitle: Stress increases blood beta-hydroxybutyrate levels and prefrontal cortex NLRP3 activity jointly in a rodent model
Creators: Tsuyoshi Nishiguchi - Faculty of Medicine, Department of Neuropsychiatry, Tottori University, Yonago, Japan
Masaaki Iwata - Faculty of Medicine, Department of Neuropsychiatry, Tottori University, Yonago, Japan
Naofumi Kajitani - Faculty of Medicine, Department of Neuropsychiatry, Tottori University, Yonago, Japan
Akihiko Miura - Faculty of Medicine, Department of Neuropsychiatry, Tottori University, Yonago, Japan
Ryoichi Matsuo - Faculty of Medicine, Department of Neuropsychiatry, Tottori University, Yonago, Japan
Shumei Murakami - Faculty of Medicine, Department of Neuropsychiatry, Tottori University, Yonago, Japan
Yumeto Nakada - Division of Clinical Laboratory, Tottori University Hospital, Tottori, Japan
Shenghong Pu - Faculty of Medicine, Department of Neuropsychiatry, Tottori University, Yonago, Japan
Yuki Shimizu - Faculty of Medicine, Department of Neuropsychiatry, Tottori University, Yonago, Japan
Tatsuya Tsubakino - Faculty of Medicine, Department of Neuropsychiatry, Tottori University, Yonago, Japan
Takehiko Yamanashi - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Gen Shinozaki - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Jun Tsubota - Energy Technology Laboratories, Osaka Gas Co., Ltd., Osaka, Japan
Yukihiko Shirayama - Department of Psychiatry, Teikyo University Chiba Medical Center, Ichihara, Japan
Ken Watanabe - Watanabe Hospital, Tottori, Japan
Koichi Kaneko - Faculty of Medicine, Department of Neuropsychiatry, Tottori University, Yonago, Japan
Resource Type: Journal article
Publication Details: Neuropsychopharmacology reports, Vol.41(2), pp.159-167
DOI: 10.1002/npr2.12164
PMID: 33609086
PMCID: PMC8340844
NLM abbreviation: Neuropsychopharmacol Rep
ISSN: 2574-173X
eISSN: 2574-173X
Publisher: United States
Grant note: JP17K10273 / JSPS SENSHIN Medical Research Foundation
Language: English
Date published: 02/20/2021
Academic Unit: Psychiatry; Iowa Neuroscience Institute; Anesthesia; Neurosurgery
Record Identifier: 9984070747602771

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