Varela Roger B, Resende Wilson R, Dal-Pont Gustavo C, Gava Fernanda F, Tye Susannah J, Quevedo João, Valvassori Samira S
Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia; Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC) -, Criciúma, SC, Brazil.
Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC) -, Criciúma, SC, Brazil.
Pharmacol Biochem Behav. 2020 Jun;193:172917. doi: 10.1016/j.pbb.2020.172917. Epub 2020 Mar 25.
The etiology of bipolar disorder (BD) is multifactorial, involving both environmental and genetic factors. Current pharmacological treatment is associated with several side effects, which are the main reason patients discontinue treatment. Epigenetic alterations have been studied for their role in the pathophysiology of BD, as they bridge the gap between gene and environment.
Evaluate the effects of histone deacetylase inhibitors on behavior and epigenetic enzymes activity in a rat model of mania induced by ouabain.
Adult male rats were subjected to a single intracerebroventricular injection of ouabain (10 M) followed by 7 days of valproate (200 mg/kg) or sodium butyrate (600 mg/kg) administration. Locomotor and exploratory activities were evaluated in the open-field test. Histone deacetylase, DNA methyltransferase, and histone acetyltransferase activity were assessed in the frontal cortex, hippocampus, and striatum.
Ouabain induced hyperactivity in rats, which was reversed by valproate and sodium butyrate treatment. Ouabain did not alter the activity of any of the enzymes evaluated. However, valproate and sodium butyrate decreased the activity of histone deacetylase and DNA methyltransferase. Moreover, there was a positive correlation between these two enzymes.
These results suggest that targeting epigenetic mechanisms may play an important role in mania-like behavior management.
双相情感障碍（BD）的病因是多因素的，涉及环境和遗传因素。目前的药物治疗伴有多种副作用，这是患者停止治疗的主要原因。表观遗传改变因其在BD病理生理学中的作用而受到研究，因为它们填补了基因与环境之间的空白。
评估组蛋白去乙酰化酶抑制剂对哇巴因诱导的大鼠躁狂模型行为和表观遗传酶活性的影响。
成年雄性大鼠经脑室内单次注射哇巴因（10 μM），随后给予丙戊酸盐（200 mg/kg）或丁酸钠（600 mg/kg）7天。在旷场试验中评估运动和探索活动。在额叶皮质、海马体和纹状体中评估组蛋白去乙酰化酶、DNA甲基转移酶和组蛋白乙酰转移酶的活性。
哇巴因诱导大鼠活动亢进，丙戊酸盐和丁酸钠治疗可使其逆转。哇巴因未改变所评估的任何酶的活性。然而，丙戊酸盐和丁酸钠降低了组蛋白去乙酰化酶和DNA甲基转移酶的活性。此外，这两种酶之间存在正相关。
这些结果表明，针对表观遗传机制可能在躁狂样行为管理中发挥重要作用。
