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

β-羟基丁酸是一种内源性 NLRP3 炎症小体抑制剂,可减轻啮齿动物创伤后应激障碍模型中的焦虑相关行为

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作者: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

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.

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