Evidence Details for Mecp2
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: Finally, the expression of Nr4a1, Rasgrp1, Rassf1, and Chkb mRNA increased in the neuronal cells treated with Mecp2 small interfering RNA.
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: Because Mecp2 and Dnmt familial genes are known as the major players in the DNA methylation process, we investigated whether methylation and mRNA expression in these genes showed a different pattern.
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: Furthermore, we investigated mRNA expression levels of Mecp2 and Dnmt familial genes in the PFC.
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: Acupuncture reversed 5-mC, MeCP2, and DNMT expression changes in the prefrontal cortex after PSNL
Evidence Sentence: To confirm the 5-mC and MeCP2 expression levels in the PFC neuron after acupuncture treatment (3 days/week for 6 months), 5-mC (Fig.
Evidence Sentence: 7A) and MeCP2 (Fig.
Evidence Sentence: One-way ANOVA with the Newman-Keuls post hoc test for 5-mC- (F[3, 20] = 16.07, P < 0.0001) and MeCP2-positive NeuN cells (F[3, 20] = 34.71, P < 0.0001) in mice with PSNL-induced neuropathic pain demonstrated that AP treatment significantly increased global DNA methylation in the PFC (5-mC, P < 0.001; MeCP2, P < 0.001 vs PSNL), but DNA methylation in the PFC was not changed in the CP group compared to that in the PSNL group (Figs.
Evidence Sentence: Mecp2 small interfering RNA increased cell death and cell growth-related genes in the primary cortical neuron cells
Evidence Sentence: To determine the causal relationship between Mecp2 and Nr4a1, Rasgrp1, Rassf1, and Chkb, we observed the Mecp2 mRNA expression in neuronal cells treated with Mecp2 siRNA.
Evidence Sentence: Unpaired two-tailed t-tests revealed that the Mecp2 mRNA expression (t4 = 9.500, P = 0.0007) in Mecp2 siRNA group was significantly lower than that in the Control group (P < 0.001; Fig.
Evidence Sentence: In addition, we found that the expression of Nr4a1 (t4 = 10.06, P = 0.0006), Rasgrp1 (t4 = 4.478, P = 0.0110), Rassf1 (t4 = 6.685, P = 0.0026), and Chkb (t4 = 4.234, P = 0.0133) was significantly increased as a result of the Mecp2 siRNA treatment (Nr4a1, P < 0.001; Chkb, P < 0.05; Rasgrp1, P < 0.05; Rassf1, P < 0.01 vs Control; Figs.