Beta-hydroxybutyrate, an endogenous NLRP3 inflammasome inhibitor, attenuates anxiety-related behavior in a rodent post-traumatic stress disorder model

Takehiko Yamanashi, Masaaki Iwata, Midori Shibushita, Kyohei Tsunetomi, Mayu Nagata, Naofumi Kajitani, Akihiko Miura, Ryoichi Matsuo, Tsuyoshi Nishiguchi, Takahiro A. Kato, Daiki Setoyama, Yukihiko Shirayama, Ken Watanabe, Gen Shinozaki, Koichi Kaneko

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1 Citation (Scopus)

Abstract

Accumulating evidence suggests that elevated inflammation contributes to the pathophysiology of post-traumatic stress disorder (PTSD) and that anti-inflammatory drugs might be a new treatment strategy for PTSD. It has been reported that beta-hydroxybutyrate (BHB), one of the main ketone bodies produced, can have an anti-inflammatory and antidepressant effect. Here, we investigated the potential anti-anxiety and anti-inflammatory effects of BHB using a rodent PTSD model, induced by single prolonged stress (SPS). Male, Sprague–Dawley rats were employed in this study. Repeated administration of BHB attenuated SPS-induced anxiety-related behaviors evaluated by the elevated plus maze test. SPS increased the serum levels of TNF-α and IL-1β. In contrast, BHB administration partially attenuated the increase of serum TNF-α. These findings demonstrate that BHB exerts its anxiolytic effects, possibly by inhibiting systemic TNF-α. Hence, BHB may be a novel therapeutic candidate for the treatment of PTSD.

Original languageEnglish
Article number21629
JournalScientific reports
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 2020

All Science Journal Classification (ASJC) codes

  • General

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