Evidence Details for Mapt
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: 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.
Evidence Sentence: PEA significantly decreases the levels of phosphorylated tau in the DRN in the rat model of D-gal-induced aging
Evidence Sentence: Intraperitoneal injection with D-gal increased tau-5, PHF-1 and tau-pS262 levels in the DRN compared with the control group (P < 0.01).
Evidence Sentence: Compared with the model group, the expression of tau-5, PHF-1 and tau-pS262 were significantly decreased in the PEA + inhibitor, PMA and PEA groups (P < 0.01), but no statistically significant difference was observed between the model and inhibitor groups (P > 0.05).
Evidence Sentence: The expression levels of tau-5 (P < 0.01) and tau-pS262 (P < 0.05) were lower in the PEA group than in the PMA group (Figure 2).
Evidence Sentence: These results indicate that PMA and PEA treatments reduce the levels of total tau (tau-5), PHF-1 and tau-pS262.
Evidence Sentence: To investigate the mechanism underlying D-gal-induced tau hyperphosphorylation, western blotting was performed to detect the expression levels of GSK-3beta and to assess its activation state.
Evidence Sentence: These results indicate that PMA and PEA treatments both inhibit the activity of GSK-3beta, thereby decreasing tau phosphorylation levels in the DRN in the rat model of D-gal-induced aging.
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: These findings indicate that PEA and PMA treatments inhibit the transcription of the GSK-3beta gene in the DRN, in turn decreasing tau phosphorylation levels, in the rat model of D-gal-induced aging.