Li Hai-Yan, Jiang Qing-Song, Fu Xiao-Yan, Jiang Xin-Hui, Zhou Qi-Xin, Qiu Hong-Mei
aKey Laboratory of Biochemistry and Molecular Pharmacology, Department of Pharmacology bKey Laboratory of Biochemistry and Molecular Pharmacology, Department of Drug Analysis, School of Pharmacy of Chongqing Medical University, Chongqing, China.
Neuroreport. 2017 Nov 8;28(16):1054-1060. doi: 10.1097/WNR.0000000000000879.
Depression is a complex multifactorial mental disorder. Its etiology involves many factors such as social environments, genetics, and psychology. Recent studies have shown that epigenetic modification may be associated with depression. Histone acetylation is one of the main mechanisms of epigenetic modification and plays an important role in genetic expression. In this study, we investigated the role of histone acetylation in the depression-like behaviors of rats undergoing chronically unpredicted stress (CUS) by detecting the mRNA and protein expression of histone deacetylase 5, cAMP-response element-binding protein, and the level of histone acetylated modification of H3K14, H3K23, and H4K16 in the prefrontal cortex and hippocampus of the rats. The results showed that significantly increasing depression-like behaviors were observed with a decreasing histone acetylated modification level, especially on acytelated-H3K14, acytelated-H3K23, and acytelated-H4K16, upregulating histone deacetylase 5 expression and downregulating cAMP-response element-binding protein expression in CUS rats, compared with control rats. The results indicate that the decrease in the histone acetylation modification level may be partly involved in the mechanism of depression-like behaviors of rats induced by CUS.
抑郁症是一种复杂的多因素精神障碍。其病因涉及社会环境、遗传学和心理学等诸多因素。最近的研究表明，表观遗传修饰可能与抑郁症有关。组蛋白乙酰化是表观遗传修饰的主要机制之一，在基因表达中起重要作用。在本研究中，我们通过检测大鼠前额叶皮质和海马中组蛋白去乙酰化酶5、环磷酸腺苷反应元件结合蛋白的mRNA和蛋白表达以及H3K14、H3K23和H4K16的组蛋白乙酰化修饰水平，研究了组蛋白乙酰化在经历慢性不可预测应激（CUS）的大鼠抑郁样行为中的作用。结果表明，与对照大鼠相比，CUS大鼠的组蛋白乙酰化修饰水平降低，尤其是乙酰化-H3K14、乙酰化-H3K23和乙酰化-H4K16，同时上调组蛋白去乙酰化酶5的表达并下调环磷酸腺苷反应元件结合蛋白的表达，抑郁样行为显著增加。结果表明，组蛋白乙酰化修饰水平的降低可能部分参与了CUS诱导的大鼠抑郁样行为的机制。
