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

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.
Authors	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
Journal	Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 21629 (12 10 2020) ISSN: 2045-2322 [Electronic] England
PMID	33303808 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Inflammasomes NLR Family, Pyrin Domain-Containing 3 Protein Nlrp3 protein, rat Tumor Necrosis Factor-alpha 3-Hydroxybutyric Acid
Topics	3-Hydroxybutyric Acid (administration & dosage, blood) Animals Anxiety (etiology, prevention & control) Disease Models, Animal Inflammasomes (antagonists & inhibitors) Injections, Subcutaneous Male NLR Family, Pyrin Domain-Containing 3 Protein (antagonists & inhibitors) Rats Rats, Sprague-Dawley Stress Disorders, Post-Traumatic (complications) Tumor Necrosis Factor-alpha (antagonists & inhibitors)

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