Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Dec 26, 2020; 12(12): 1576-1590
Published online Dec 26, 2020. doi: 10.4252/wjsc.v12.i12.1576
Acupuncture accelerates neural regeneration and synaptophysin production after neural stem cells transplantation in mice
Lan Zhao, Jian-Wei Liu, Bo-Hong Kan, Hui-Yan Shi, Lin-Po Yang, Xin-Yu Liu
Lan Zhao, Bo-Hong Kan, Hui-Yan Shi, Lin-Po Yang, Xin-Yu Liu, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
Lan Zhao, Bo-Hong Kan, Hui-Yan Shi, Tianjin Key Laboratory of Acupuncture and Moxibustion, Tianjin 300381, China
Lan Zhao, Bo-Hong Kan, Hui-Yan Shi, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China
Jian-Wei Liu, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
Author contributions: Zhao L was responsible for the study design and research funding, and wrote the manuscript; Zhao L and Liu J performed the neural stem cell transplantation; Shi HY was responsible for acupuncture; Kan BH and Yang LP were involved in the data collection; Liu XY and Kan BH performed statistical analysis and some of the experiments; all authors approved the final version of the manuscript.
Supported by National Natural Science Foundation of China, No. 81202740; and Tianjin Natural Science Fund, No. 17JCYBJC26200.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (approval number: TCM-LAEC2019036).
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at lanzhao69@163.com. Participants gave informed consent for data sharing.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lan Zhao, PhD, Research Fellow, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine; Tianjin Key Laboratory of Acupuncture and Moxibustion; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, No. 88 Changling Road, Xiqing District, Tianjin 300381, China. lanzhao69@163.com
Received: February 27, 2020
Peer-review started: February 27, 2020
First decision: September 11, 2020
Revised: September 23, 2020
Accepted: October 13, 2020
Article in press: October 13, 2020
Published online: December 26, 2020
Abstract
BACKGROUND

Synaptophysin plays a key role in synaptic development and plasticity of neurons and is closely related to the cognitive process of Alzheimer’s disease (AD) patients. Exogenous neural stem cells (NSCs) improve the damaged nerve function. The effects of Sanjiao acupuncture on cognitive impairment may be related to the regulation of the NSC microenvironment.

AIM

To explore the anti-dementia mechanism of acupuncture by regulating the NSC microenvironment.

METHODS

NSCs were isolated from pregnant senescence-accelerated mouse resistant 1 (SAMR1) mice, labeled with BrdU, and injected into the hippocampus of senescence-accelerated mouse prone 8 (SAMP8) mice. Eight-month-old senescence-accelerated mice (SAM) were randomly divided into six groups: SAMR1 (RC), SAMP8 (PC), sham transplantation (PS), NSC transplantation (PT), NSC transplantation with acupuncture (PTA), and NSC transplantation with non-acupoint acupuncture (PTN). Morris water maze test was used to study the learning and memory ability of mice after NSC transplantation. Hematoxylin-eosin staining and immunofluorescence were used to observe the his-topathological changes and NSC proliferation in mice. A co-culture model of hippocampal slices and NSCs was established in vitro, and the synaptophysin expression in the hippocampal microenvironment of mice was observed by flow cytometry after acupuncture treatment.

RESULTS

Morris water maze test showed significant cognitive impairment of learning and memory in 8-mo-old SAMP8, which improved in all the NSC transplantation groups. The behavioral change in the PTA group was stronger than those in the other two groups (P < 0.05). Histopathologically, the hippocampal structure was clear, the cell arrangement was dense and orderly, and the necrosis of cells in CA1 and CA3 areas was significantly reduced in the PTA group when compared with the PC group. The BrdU-positive proliferating cells were found in NSC hippocampal transplantation groups, and the number increased significantly in the PTA group than in the PT and PTN groups (P < 0.05). Flow cytometry showed that after co-culture of NSCs with hippocampal slices in vitro, the synaptophysin expression in the PC group decreased in comparison to the RC group, that in PT, PTA, and PTN groups increased as compared to the PC group, and that in the PTA group increased significantly as compared to the PTN group with acupoint-related specificity (P < 0.05).

CONCLUSION

Acupuncture may promote nerve regeneration and synaptogenesis in SAMP8 mice by regulating the microenvironment of NSC transplantation to improve the nerve activity and promote the recovery of AD-damaged cells.

Keywords: Neurodegeneration, Alzheimer's disease, Neural stem cells, Micro-environment, Synaptophysin, Acupuncture

Core Tip: Neural stem cells (NSCs) transplantation offers high hopes for clinical therapy of Alzheimer’s disease. Our previous studies suggested that Sanjiao acupuncture might affect some materials in the NSCs microenvironment. In order to study whether acupuncture can play a positive role in neuron regeneration by acting on the microenvironment of exogenous neural stem cells, in this study, we observed the effects of Sanjiao acupuncture on neural regeneration and synaptophysin production in senescence-accelerated mouse prone 8 mice with grafted exogenous NSCs.