Antidepressant-Like Effects of Acupuncture-Insights From DNA Methylation and Histone Modifications of Brain-Derived Neurotrophic Factor.

Huili Jiang,Bingcong Zhao,Yang Sun,Xinjing Yang,Hong Meng,Tuya Bao,Xuhui Zhang,Jun Lu

doi:10.3389/fpsyt.2018.00102

Abstract

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.

Highlights

Depression, one of the most prevalent psychiatric disorders, is considered to be one of the leading causes of disability [1, 2]
There were no significant differences in responses to body weight (BW) gain between fluoxetine and acupuncture groups (Figure 3A)
Through analyzing the expression levels of brain-derived neurotrophic factor (BDNF) mRNA, acH3K9 and HDAC2, and the DNA methylation level of BDNF promoter I at relative CpG sites in hippocampus, we identified that DNA methylation and histone modifications of BDNF in the hippocampus were involved in the pathological process of depression (Figures 4H,I)

Summary

Introduction

Depression, one of the most prevalent psychiatric disorders, is considered to be one of the leading causes of disability [1, 2]. Increasing evidence suggests that chronic stress is one of the leading contributing factors in the development, maintenance, or exacerbation of depression [3,4,5,6]. The Antidepressant-Like Effects of Acupuncture via the Expression of BDNF that the systemic perturbations of homeostasis could induce the dysfunction of abnormalities in regional brain activity [7, 8], impaired neurogenesis, and changes in synaptic function [9,10,11,12]. Chronic stress to genetically vulnerable individuals might induce the dysfunctions of neurogenesis and synaptic function, or a significant reduction of brain-derived neurotrophic factor (BDNF) expression [17, 18]. Data from clinical investigations and laboratory animals have provided compelling evidence that BDNF is involved in the pathogenesis of depression [19,20,21]

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