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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. |
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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). |
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The DNA methylation patterns of the promoter I of BDNF was detected by MS-PCR. |
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We investigated that the expression of BDNF in serum and hippocampus were significantly downregulated compared with controls. |
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The same trend was found in mRNA of BDNF. |
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Notably, acupuncture reversed the downregulation of BDNF in serum and hippocampus and mRNA of BDNF compared with model group. |
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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. |
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Expression Level of BDNF in Serum |
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Compared with the control group, the expression of BDNF in serum in the model group was significantly downregulated (P < 0.01). |
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Following the intervention of acupuncture and fluoxetine, the expression of BDNF in serum in acupuncture and FLXs were significantly upregulated compared with that in the model group (P < 0.01; P < 0.01) (Figure 4A). |
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Both acupuncture and fluoxetine could reverse the downregulation of BDNF in serum induced by CUMS. |
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Expression Level of BDNF in the Hippocampus |
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The result showed that, compared with the control group, the expression of hippocampal BDNF in the model group was significantly downregulated (P < 0.01). |
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Of note, acupuncture reversed the downregulation of hippocampal BDNF when compared with that in the model group with statistical significance (P < 0.01). |
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There were no significant differences in the expression of hippocampal BDNF between fluoxetine and model group (P > 0.05) (Figure 4B). |
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Expression of mRNA Level of BDNF in the Hippocampus |
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The results indicated that the relative mRNA expression level of BDNF in the hippocampus of the model group was significantly lower than that in the control group (P < 0.01). |
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In comparison with the model group, the lower expression of mRNA levels of BDNF was significantly reversed in the acupuncture and FLXs following the intervention of acupuncture and fluoxetine (P < 0.01; P < 0.01). |
| Evidence Sentence: |
Importantly, the relative mRNA expression level of BDNF in the hippocampus of the acupuncture group was evidently higher than that in the FLX (Figure 4C). |
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The DNA Methylation Level of Hippocampal BDNF Promoter I Corresponding to 12 CpG Sites |
| Evidence Sentence: |
In this study, the DNA methylation level of hippocampal BDNF promoter I was assessed at 12 CpG sites, including CpG2, CpG4, CpG 5, CpG6, CpG10, CpG11, CpG12, CpG13, CpG14, CpG15, CpG16, CpG18, and CpG24, as detected by MS-PCR. |
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In comparison with the DNA methylation level of BDNF promoter I at relative CpG sites, no significant differences have been found among control, model, acupuncture, and FLXs recently (P > 0.05). |
| Evidence Sentence: |
The precise mechanisms that the DNA methylation level of BDNF promoter I are involved in the pathogenesis of depression remains to be further clarified (Figure 4D). |
