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World J Stem Cells. Mar 26, 2026; 18(3): 114929
Published online Mar 26, 2026. doi: 10.4252/wjsc.v18.i3.114929
Published online Mar 26, 2026. doi: 10.4252/wjsc.v18.i3.114929
Acupuncture improves transplanted neural stem cells in dementia mice by modulating hippocampal microenvironment via microRNA-124 mediated Notch and Wnt pathways
Yu-Jiao Li, Xi Chen, Yong-Yin Luo, Jun Chang, Shu-Zhen Liu, Xiao-Qian Shan, Jing-Jing Song, Nan Hao, Xu-He Yan, Wei-Li Gao, Lan Zhao, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine, Tianjin 300381, China
Jian-Wei Liu, School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Co-first authors: Yu-Jiao Li and Xi Chen.
Co-corresponding authors: Jian-Wei Liu and Lan Zhao.
Author contributions: Zhao L contributed to the conceptualization, funding acquisition, project administration, and supervision; Liu JW contributed to the conceptualization, animal modeling and supervision; Li YJ, Chen X, Luo YY, Chang J, Shan XQ, and Song JJ contributed to investigation and methodology; Li YJ and Chen X contributed to writing original draft; Liu SZ, Hao N, Yan XH, and Gao WL contributed to writing-review and editing. All authors have read and agreed to the published version of the manuscript. We designated Zhao L and Liu JW as co-corresponding authors for three key reasons. First, the study’s collaborative nature warrants shared responsibility, ensuring effective post-submission communication and enhancing the paper’s quality. Second, both authors possess complementary expertise, enriching the research with diverse, in-depth perspectives for readers. Third, Zhao L and Liu JW contributed equally throughout the project. There are two main reasons for deciding to designate Li YJ and Chen X as co-first authors. First, this study was conducted as a collaborative effort, and it is reasonable to designate a co- author. Second, both authors contributed equally during the experimental implementation, data processing, plotting and writing of this manuscript. We believe that designating Zhao L and Liu JW as co-corresponding authors and Li YJ and Chen X as co-first authors are suitable for our manuscript as it accurately reflects our team’s spirit of cooperation, equal contribution and diversity.
Supported by National Natural Science Foundation of China, No. 82074533.
Institutional animal care and use committee statement: All procedures involving animals are reviewed and approved by the Tianjin University of Traditional Chinese Medicine, No. TCM-LAEC2022045.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.
Corresponding author: Lan Zhao, PhD, Professor, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine, No. 88 Changling Road, Xiqing District, Tianjin 300381, China. lanzhao69@163.com
Received: October 11, 2025
Revised: November 5, 2025
Accepted: January 26, 2026
Published online: March 26, 2026
Processing time: 174 Days and 20 Hours
Revised: November 5, 2025
Accepted: January 26, 2026
Published online: March 26, 2026
Processing time: 174 Days and 20 Hours
Core Tip
Core Tip: Acupuncture improved hippocampal microenvironmental dysfunction in a mouse model of Alzheimer’s disease (AD), thereby enhancing the biological activity of transplanted neural stem cells (NSCs). Acupuncture reduced AD-related pathological biomarkers and upregulated microRNA-124, which concurrently targeted Notch homolog 1, hairy and enhancer of split 5, and glycogen synthase kinase 3β, modulating the Notch and Wnt signaling pathways. This dual pathway regulated cyclin D1-mediated NSCs proliferation and differentiation, and promoted neural circuit remodeling. Consequently, AD pathology was markedly suppressed. Our study identified microRNA-124/Notch-Wnt as a promising therapeutic target and suggests that sustained acupuncture is a viable strategy for mitigating irreversible neurofunctional deficits in AD.