Jiang Huili, Zhang Xuhui, Lu Jun, Meng Hong, Sun Yang, Yang Xinjing, Zhao Bingcong, Bao Tuya
School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China.
Research Center of Mental and Neurological Disorders, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China.
Front Psychiatry. 2018 Mar 27;9:102. doi: 10.3389/fpsyt.2018.00102. eCollection 2018.
Sensitive and stable biomarkers that facilitate depression detection and monitor the antidepressant efficiency are currently unavailable. Thus, the objective is to investigate the potential of DNA methylation and histone modifications of brain-derived neurotrophic factor (BDNF) in monitoring severity and antidepressive effects of acupuncture. The depression rat model was imitated by social isolation and chronic unpredicted mild stress (CUMS). The expression of serum BDNF was detected by enzyme-linked immunosorbent assay (ELISA), the hippocampal BDNF, acetylation levels in histone H3 lysine 9 (acH3K9), and HDAC2 by Western blot, the hippocampal mRNA of BDNF by RT-polymerase chain reaction (PCR). The DNA methylation patterns of the promoter I of BDNF was detected by MS-PCR. We investigated that the expression of BDNF in serum and hippocampus were significantly downregulated compared with controls. The same trend was found in mRNA of BDNF. Notably, acupuncture reversed the downregulation of BDNF in serum and hippocampus and mRNA of BDNF compared with model group. Acupuncture reversed the CUMS-induced downregulation of hippocampal acH3K9. On the contrary, the CUMS-induced upregulation of hippocampal HDAC2 in model group was significantly reversed by acupuncture. Collectively, the antidepressant effect of acupuncture might be mediated by regulating the DNA methylation and histone modifications of BDNF, which may represent novel biomaker for detection of depression and monitoring severity and antidepressive effects.
目前尚不存在能够促进抑郁症检测并监测抗抑郁药疗效的敏感且稳定的生物标志物。因此，本研究旨在探讨脑源性神经营养因子（BDNF）的DNA甲基化和组蛋白修饰在监测针灸治疗抑郁症的严重程度及抗抑郁效果方面的潜力。采用社会隔离和慢性不可预测温和应激（CUMS）方法建立抑郁症大鼠模型。采用酶联免疫吸附测定（ELISA）检测血清BDNF表达水平，蛋白质免疫印迹法检测海马BDNF、组蛋白H3赖氨酸9（acH3K9）乙酰化水平及HDAC2表达水平，逆转录聚合酶链反应（RT-PCR）检测海马BDNF mRNA表达水平。采用甲基化特异性PCR（MS-PCR）检测BDNF启动子I的DNA甲基化模式。研究发现，与对照组相比，模型组血清和海马中BDNF的表达均显著下调，BDNF mRNA表达也呈相同趋势。值得注意的是，与模型组相比，针刺可逆转血清和海马中BDNF及BDNF mRNA的下调。针刺可逆转CUMS诱导的海马acH3K9下调。相反，针刺可显著逆转模型组中CUMS诱导的海马HDAC2上调。综上所述，针刺的抗抑郁作用可能是通过调节BDNF的DNA甲基化和组蛋白修饰来介导的，这可能代表了用于检测抑郁症以及监测其严重程度和抗抑郁效果的新型生物标志物。
