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单相和双相抑郁症患者褪黑素受体的甲基化

Methylation of melatonin receptors in patients with unipolar and bipolar depression.

作者信息

Lesicka Monika, Dmitrzak-Weglarz Monika, Jablonska Ewa, Wieczorek Edyta, Kapelski Pawel, Szczepankiewicz Aleksandra, Pawlak Joanna, Reszka Edyta

机构信息

Department of Translational Research, Nofer Institute of Occupational Medicine, Lodz, Poland.

Department of Psychiatric Genetics, Department of Psychiatry, University of Medical Sciences, Poznan, Poland.

出版信息

Mech Ageing Dev. 2023 Apr;211:111776. doi: 10.1016/j.mad.2023.111776. Epub 2023 Jan 24.

Abstract

Disturbances of melatonin secretion alter the circadian rhythm and sleep-wake cycle, which is observed among patients with depression. Melatonin acts via melatonin receptors MT1 and MT2, which are present in many tissues, including peripheral blood mononuclear cells (PBMC). We assume that disturbances of the melatonin pathway in the brain may be reflected by molecular changes in peripheral organs. The study objective was to evaluate the methylation profile of CpG island in the promoter region of melatonin receptor genes MTNR1A and MTNR1B in PBMC of patients with depression and compare it with healthy volunteers. The study group comprised 85 patients with unipolar (UP) and bipolar disorders (BP) and 83 controls. The methylation pattern of CpG island in the promoter region was analyzed using the quantitative methylation-specific real-time PCR (qMSP-PCR) method. We found that the methylation profile of the patients with depression varied in comparison to the control group. The methylation level of MTNR1A was significantly lower among depressed patients compared to controls. Additionally, melatonin concentration was negatively correlated with MTNR1B methylation level among the UP patients. The study may suggest that the methylation profile of melatonin receptors in PBMC may be used as a complementary molecular marker in depression diagnosis.

摘要

褪黑素分泌紊乱会改变昼夜节律和睡眠-觉醒周期,这在抑郁症患者中很常见。褪黑素通过褪黑素受体MT1和MT2发挥作用,这些受体存在于包括外周血单核细胞(PBMC)在内的许多组织中。我们假设大脑中褪黑素通路的紊乱可能会在外周器官的分子变化中得到体现。本研究的目的是评估抑郁症患者PBMC中褪黑素受体基因MTNR1A和MTNR1B启动子区域CpG岛的甲基化谱,并将其与健康志愿者进行比较。研究组包括85例单相(UP)和双相情感障碍(BP)患者以及83名对照。使用定量甲基化特异性实时PCR(qMSP-PCR)方法分析启动子区域CpG岛的甲基化模式。我们发现,与对照组相比,抑郁症患者的甲基化谱有所不同。与对照组相比,抑郁症患者中MTNR1A的甲基化水平显著降低。此外,在单相抑郁症患者中,褪黑素浓度与MTNR1B甲基化水平呈负相关。该研究可能表明,PBMC中褪黑素受体的甲基化谱可作为抑郁症诊断的补充分子标志物。

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