Evidence Details for Dnmt1
| PMID | Title | Journal | Year | Abstract |
|---|---|---|---|---|
| 33229729 | Preventive electroacupuncture reduces cognitive deficits in a rat model of D-galactose-induced aging. | Neural Regen Res. 2021 May;16(5):916-923. doi: 10.4103/1673-5374.297090. | 2021 May | Acupuncture can reduce cognitive deficits in Alzheimer's disease. However, whether electroacupuncture can prevent or alleviate the cognitive deficits in animal models of aging remains poorly understood. Studies have shown that disordered epigenetic modifications play a critical role in age-related cognitive decline. Therefore, we hypothesized that preventive electroacupuncture might improve cognitive functions during aging by regulating epigenetic modifications. A rat model of aging was produced by intraperitoneal injection of 120 mg/kg D-galactose for 8 weeks. Baihui and Shenshu acupoints were stimulated by electroacupuncture for 8 weeks from the first day of D-galactose administration. Preventive electroacupuncture alleviated memory impairment, decreased tau hyperphosphorylation, and reduced glycogen synthase kinase-3beta protein and mRNA expression levels in the brainstem dorsal raphe nucleus, where intracellular neurofibrillary tangle lesions first occur. In addition, the DNA methylation level in the promoter region of the glycogen synthase kinase-3beta gene was increased. The effects of preventive electroacupuncture were stronger than those of preventive acupuncture. Intraperitoneal injection of 0.4 mg/kg 5-aza-2'-deoxycytidine, an inhibitor of DNA methyltransferase that blocks epigenetic modifications, antagonized the effects of preventive electroacupuncture. Our results suggest that preventive electroacupuncture treatment alleviates cognitive impairment in aging rats probably by affecting the epigenetic modification of the glycogen synthase kinase-3beta gene in the dorsal raphe nucleus. This study was approved by the Animal Ethics Committee of Hubei University of Chinese Medicine, China (approval No. HUCMS201712001) on November 28, 2017." |
| Evidence Sentence: | In the present study, we observed that the DNMT inhibitor 5-aza-2'-deoxycytidine aggravated memory dysfunction, synaptic damage and tau hyperphosphorylation, and that PEA treatment ameliorated the synaptic morphological changes and restored cognitive function, suggesting that modulation of DNA methylation might be involved in the neuroprotective effect of PEA. |
| Evidence Sentence: | PEA and PMA increase the expression of DNMT1 in the DRN in the rat model of D-gal-induced aging |
| Evidence Sentence: | Next, we studied the expression of DNMT1 in the DRN in rats with D-gal-induced aging. |
| Evidence Sentence: | As shown in Figure 5, the expression of DNMT1 in the DRN was significantly decreased in the rat model of D-gal-induced aging. |
| Evidence Sentence: | Compared with the model group, the expression of DNMT1 in the inhibitor group was decreased (P < 0.05 in immunofluorescence staining, P < 0.05 in western blot assay), but increased in the PEA + inhibitor (P < 0.01 in immunofluorescence staining, P < 0.05 in western blot assay), PMA (P < 0.01 in immunofluorescence staining, P < 0.05 in western blot) and PEA groups (P < 0.01 in immunofluorescence staining, P < 0.05 in western blot). |
| Evidence Sentence: | In addition, the expression levels of DNMT1 were decreased in the PEA + inhibitor (P < 0.01 in immunofluorescence staining, P < 0.01 in western blot assay), inhibitor (P < 0.01 in immunofluorescence staining, P < 0.01 in western blot) and PMA groups (P < 0.05 in immunofluorescence staining, P < 0.05 in western blot assay) compared with the PEA group. |
| Evidence Sentence: | These results indicate that PEA increases GSK-3beta DNA methylation levels by upregulating the expression of DNMT1, and that PEA is more effective than PMA. |