Seki Tomoe, Yamagata Hirotaka, Uchida Shusaku, Chen Chong, Kobayashi Ayumi, Kobayashi Masaaki, Harada Kenichiro, Matsuo Koji, Watanabe Yoshifumi, Nakagawa Shin
Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan.
Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan.
J Psychiatr Res. 2019 Oct;117:92-99. doi: 10.1016/j.jpsychires.2019.07.004. Epub 2019 Jul 19.
Although major depressive disorder (MDD) is a leading cause of disability worldwide, its pathophysiology is poorly understood. Increasing evidence suggests that aberrant regulation of transcription plays a key role in the pathophysiology of MDD. Recently, long noncoding RNAs (lncRNAs) have been recognized for their important functions in chromatin structure, gene expression, and the subsequent manifestation of various biological processes in the central nervous system. However, it is unclear whether the aberrant expression and function of lncRNAs are associated with the pathophysiology of MDD. In this study, we sought to evaluate the expression of lncRNAs in peripheral blood leukocytes as potential biomarkers for MDD. We measured the expression levels of 83 lncRNAs in the peripheral blood leukocytes of 29 MDD patients and 29 age- and gender-matched healthy controls using quantitative reverse transcription PCR (RT-qPCR) analysis. We found that MDD patients exhibited distinct expression signatures. Specifically, the expression level of one lncRNA (RMRP) was lower while the levels of four (Y5, MER11C, PCAT1, and PCAT29) were higher in MDD patients compared to healthy controls. The expression level of RMRP was correlated with depression severity as measured by the Hamilton Depression Rating Scale (HAM-D). Moreover, RMRP expression was lower in a mouse model of depression, corroborating the observation from MDD patients. Taken together, our data suggest that lower RMRP levels may serve as a potential biomarker for MDD.
尽管重度抑郁症(MDD)是全球致残的主要原因,但其病理生理学仍知之甚少。越来越多的证据表明,转录异常调控在MDD的病理生理学中起关键作用。最近,长链非编码RNA(lncRNAs)因其在染色质结构、基因表达以及中枢神经系统各种生物过程的后续表现中的重要功能而受到认可。然而,尚不清楚lncRNAs的异常表达和功能是否与MDD的病理生理学相关。在本研究中,我们试图评估外周血白细胞中lncRNAs的表达,作为MDD的潜在生物标志物。我们使用定量逆转录PCR(RT-qPCR)分析测量了29例MDD患者和29例年龄及性别匹配的健康对照外周血白细胞中83种lncRNAs的表达水平。我们发现MDD患者表现出独特的表达特征。具体而言,与健康对照相比,MDD患者中一种lncRNA(RMRP)的表达水平较低,而四种(Y5、MER11C、PCAT1和PCAT29)的表达水平较高。RMRP的表达水平与汉密尔顿抑郁量表(HAM-D)测量的抑郁严重程度相关。此外,在抑郁症小鼠模型中RMRP表达较低,这证实了来自MDD患者的观察结果。综上所述,我们的数据表明较低的RMRP水平可能作为MDD的潜在生物标志物。