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Acupuncture improves transplanted neural stem cells in dementia mice by modulating hippocampal microenvironment via microRNA-124 mediated Notch and Wnt pathways
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DOI:10.4252/wjsc.v18.i3.114929.png)
Abstract
En 中文
BACKGROUND Neural stem cells (NSCs) transplantation is a promising clinical therapy for Alzheimer's disease (AD). The Notch and Wnt signaling pathways play important roles in the biological functions of NSCs, and microRNA-124 (miR-124) regulates these pathways through its regulatory effects. AIM To explore the mechanism of acupuncture in enhancing the function of transplanted NSCs and their therapeutic potential in AD. METHODS This study utilized enzyme-linked immunosorbent assay, western blotting, and real-time fluorescent quantitative polymerase chain reaction, to investigate the effects of acupuncture on the role of miR-124 in regulating the Notch and Wnt signaling pathways, in NSCs transplantation therapy in a mouse model of AD-senescence-accelerated mouse prone 8 mice. An in vitro coculture model of mouse hippocampal brain slices and NSCs was established, and flow cytometry was used to examine the effects of acupuncture on the regulation of cyclin D1, an interactive protein in the Notch and Wnt signaling pathways, and on NSCs proliferation and differentiation. RESULTS Acupuncture significantly improved cognitive impairment in AD mice after NSCs transplantation (P < 0.05); inhibited expression of characteristic pathological biomarkers of AD (P < 0.05); and upregulated expression of NSCs-specific neuroproliferation and differentiation biomarkers (P < 0.05). Upregulation of miR-124 modulated the key target genes Notch homolog 1, hairy and enhancer of split 5, and glycogen synthase kinase 3 beta in the Notch and Wnt signaling pathways (P < 0.05); regulated the Notch and Wnt dual signaling pathways and achieved interaction (P < 0.05); promoted NSCs proliferation and differentiation (P < 0.05); restored damaged cells; and slowed the progression of AD. CONCLUSION Acupuncture may improve the hippocampal microenvironment by upregulating miR-124 to regulate the Notch and Wnt dual signaling pathways, promote NSCs proliferation and differentiation, facilitate the repair of damaged neurons, integrate neural circuits, restore biological functions, and improve cognitive impairment in AD mice.
Keywords:
Neural stem cells
Hippocampal microenvironment
Acupuncture
MicroRNA-124
Notch signaling pathway
Wnt signaling pathway
Alzheimer's disease
Journal
IF:
3.6
Papers:
827
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2.8K
