Department of Medical Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland.
Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
Int J Mol Sci. 2022 Aug 11;23(16):8983. doi: 10.3390/ijms23168983.
The preclinical research conducted so far suggest that depression development may be influenced by the inflammatory pathways both at the periphery and within the central nervous system. Furthermore, inflammation is considered to be strongly connected with antidepressant treatment resistance. Thus, this study explores whether the chronic mild stress (CMS) procedure and agomelatine treatment induce changes in , , , and expression and methylation status in peripheral blood mononuclear cells (PBMCs) and in the brain structures of rats. Adult male Wistar rats were subjected to the CMS and further divided into matched subgroups to receive vehicle or agomelatine. TaqMan gene expression assay and methylation-sensitive high-resolution melting (MS-HRM) were used to evaluate the expression of the genes and the methylation status of their promoters, respectively. Our findings confirm that both CMS and antidepressant agomelatine treatment influenced the expression level and methylation status of the promoter region of investigated genes in PBMCs and the brain. What is more, the present study showed that response to either stress stimuli or agomelatine differed between brain structures. Concluding, our results indicate that , , , and could be associated with depression and its treatment.
迄今为止的临床前研究表明，抑郁的发展可能受到外周和中枢神经系统炎症途径的影响。此外，炎症被认为与抗抑郁治疗的抵抗有很强的关联。因此，本研究探讨了慢性轻度应激（CMS）程序和阿戈美拉汀治疗是否会引起大鼠外周血单个核细胞（PBMC）和大脑结构中 、 、 、 和 的表达和甲基化状态的变化。成年雄性 Wistar 大鼠接受 CMS 处理，并进一步分为匹配的亚组，分别接受载体或阿戈美拉汀。TaqMan 基因表达检测和甲基化敏感高分辨率熔解（MS-HRM）分别用于评估基因的表达和启动子的甲基化状态。我们的研究结果证实，CMS 和抗抑郁药阿戈美拉汀治疗均影响了 PBMC 和大脑中研究基因启动子区域的表达水平和甲基化状态。此外，本研究还表明，对压力刺激或阿戈美拉汀的反应在不同的大脑结构之间存在差异。总之，我们的研究结果表明， 、 、 、 和 可能与抑郁及其治疗有关。
