Laboratory of Neurosciences, National Institute for Translational Medicine (INCT-TM), and Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, 88806-000, Brazil,
J Neural Transm (Vienna). 2013 Dec;120(12):1737-42. doi: 10.1007/s00702-013-1056-3. Epub 2013 Jul 14.
There is increasing interest in the possibility that mitochondrial impairment may play an important role in bipolar disorder (BD). The Krebs cycle is the central point of oxidative metabolism, providing carbon for biosynthesis and reducing agents for generation of ATP. Recently, studies have suggested that histone deacetylase (HDAC) inhibitors may have antimanic effects. The present study aims to investigate the effects of sodium butyrate (SB), a HDAC inhibitor, on Krebs cycle enzymes activity in the brain of rats subjected to an animal model of mania induced by D-amphetamine (D-AMPH). Wistar rats were first given D-AMPH or saline (Sal) for 14 days, and then, between days 8 and 14, rats were treated with SB or Sal. The citrate synthase (CS), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were evaluated in the prefrontal cortex, hippocampus, and striatum of rats. The D-AMPH administration inhibited Krebs cycle enzymes activity in all analyzed brain structures and SB reversed D-AMPH-induced dysfunction analyzed in all brain regions. These findings suggest that Krebs cycle enzymes' inhibition can be an important link for the mitochondrial dysfunction seen in BD and SB exerts protective effects against the D-AMPH-induced Krebs cycle enzymes' dysfunction.
人们越来越关注线粒体损伤在双相情感障碍（BD）中的可能作用。三羧酸循环是氧化代谢的中心点，为生物合成提供碳源，并为 ATP 的产生提供还原剂。最近的研究表明，组蛋白去乙酰化酶（HDAC）抑制剂可能具有抗躁狂作用。本研究旨在探讨组蛋白去乙酰化酶抑制剂丁酸钠（SB）对 D-amphetamine（D-AMPH）诱导的躁狂动物模型大鼠大脑中三羧酸循环酶活性的影响。Wistar 大鼠首先接受 D-AMPH 或生理盐水（Sal）治疗 14 天，然后在第 8 天至第 14 天期间接受 SB 或 Sal 治疗。在大鼠的前额叶皮层、海马体和纹状体中评估柠檬酸合酶（CS）、琥珀酸脱氢酶（SDH）和苹果酸脱氢酶（MDH）的活性。D-AMPH 给药抑制了所有分析脑结构中的三羧酸循环酶活性，而 SB 逆转了所有脑区 D-AMPH 诱导的功能障碍。这些发现表明，三羧酸循环酶的抑制可能是 BD 中线粒体功能障碍的一个重要环节，而 SB 对 D-AMPH 诱导的三羧酸循环酶功能障碍具有保护作用。
