Evidence Details for Dnmt3a
PMID Title Journal Year Abstract
32796318 Acupuncture alleviates chronic pain and comorbid conditions in a mouse model of neuropathic pain: the involvement of DNA methylation in the prefrontal cortex. Pain. 2021 Feb 1;162(2):514-530. doi: 10.1097/j.pain.0000000000002031. 2021 Feb 1 Chronic pain reduces life quality and is an important clinical problem associated with emotional and cognitive dysfunction. Epigenetic regulation of DNA methylation is involved in the induction of abnormal behaviors and pathological gene expression. We examined whether acupuncture can restore epigenetic changes caused by chronic pain, and identified the underlying mechanisms in neuropathic pain mice. Acupuncture treatment for 6 months (3 days/week) improved mechanical/cold allodynia and the emotional/cognitive dysfunction caused by left partial sciatic nerve ligation (PSNL)-induced neuropathic pain. The effects of acupuncture were associated with global DNA methylation recovery in the prefrontal cortex (PFC). Analysis of DNA methylation patterns in PFC indicated that 1364 overlapping genes among 4442 and 4416 methylated genes in the PSNL vs sham and PSNL vs acupuncture points groups, respectively, were highly associated with the DNA methylation process. Acupuncture restored the reduced expression of 5-methylcytosine, methyl-cytosine-phospho-guanine binding protein 2, and DNA methyltransferase family enzymes induced by PSNL in PFC. Methylation levels of Nr4a1 and Chkb associated with mitochondrial dysfunction were decreased in PFC of the PSNL mice, and increased by acupuncture. By contrast, high expression of Nr4a1 and Chkb mRNA in PSNL mice decreased after acupuncture. We also found that acupuncture inhibited the expression of Ras pathway-related genes such as Rasgrp1 and Rassf1. Finally, the expression of Nr4a1, Rasgrp1, Rassf1, and Chkb mRNA increased in the neuronal cells treated with Mecp2 small interfering RNA. These results suggest that acupuncture can relieve chronic pain-induced comorbid conditions by altering DNA methylation of Nr4a1, Rasgrp1, Rassf1, and Chkb in the PFC."

Evidence Sentence: Overlapping genes (1364) shared Mecp2, Dnmt1, Dnmt3a, and Dnmt3b associated with DNA methylation in DNA metabolic processes (146) and metabolic pathways (244) (Fig.
Evidence Sentence: One-way ANOVA showed a significant difference among groups in DNA methylation in the promoter regions of the Mecp2 and Dnmt familial genes (Mecp2, F[2, 6] = 5.645, P = 0.0418; Dnmt1, F[2, 6] = 6.115, P = 0.0357; Dnmt3a, F[2, 6] = 20.43, P = 0.0021; Dnmt3b, F[2, 6] = 5.012, P = 0.0525), and the Newman-Keuls post hoc test indicated that DNA methylation in the PSNL group was increased in the PFC (Mecp2, P > 0.05; Dnmt1, P > 0.05; Dnmt3a, P < 0.01; Dnmt3b, P > 0.05 vs each sham group), and was lower in the AP vs the PSNL group (Mecp2, P < 0.05; Dnmt1, P < 0.05; Dnmt3a, P < 0.01; Dnmt3b, P > 0.05 vs each PSNL group; Figs.
Evidence Sentence: One-way ANOVA indicated a significant difference among groups in the mRNA levels of Mecp2 and Dnmt familial genes (Mecp2, F[2, 6] = 2.648, P = 0.1498; Dnmt1, F[2, 6] = 11.52, P = 0.0088; Dnmt3a, F[2, 6] = 13.43, P = 0.0061; Dnmt3b, F[2, 6] = 3.276, P = 0.1092), and the Newman-Keuls post hoc test indicated that acupuncture improved mRNA expression levels that were reduced in the PSNL group (Mecp2, P > 0.05; Dnmt1, P < 0.01; Dnmt3a, P < 0.01; Dnmt3b, P > 0.05 vs each PSNL group; Figs.
Evidence Sentence: These results indicated that various genes, including Mecp2, Dnmt1, and Dnmt3a as well as those involved in the DNA methylation process, were restored by acupuncture.
Evidence Sentence: Next, to confirm the changes in DNMT enzymes associated with acupuncture treatment (3 days/week for 6 months) for PSNL-induced neuropathic pain, DNMT1, DNMT3a, and DNMT3b were examined by Western blot analysis in the PFC tissues of the mouse model.
Evidence Sentence: One-way ANOVA showed significant differences in the protein expression of DNMT1 (F[3, 12] = 10.85, P = 0.0010) and DNMT3a (F[3, 12] = 7.601, P = 0.0041) in the PFC among the 4 groups.
Evidence Sentence: The Newman-Keuls post hoc test indicated that DNMT1 and DNMT3a expression levels were significantly higher in the AP group than in the PSNL group (DNMT1, P < 0.01; DNMT3a, P < 0.05, respectively).
Evidence Sentence: The PSNL and CP groups did not show differences in DNMT1 or DNMT3a expression levels in the PFC, respectively (Figs.