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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Magnesium-L-threonate exhibited a neuroprotective effect against oxidative stress damage in HT22 cells and Alzheimer’s disease mouse model
Ying Xiong, Yu-Ting Ruan, Jing Zhao, Yu-Wen Yang, Li-Ping Chen, Ying-Ren Mai, Qun Yu, Zhi-Yu Cao, Fei-Fei Liu, Wang Liao, Jun Liu
Ying Xiong, Ying-Ren Mai, Qun Yu, Zhi-Yu Cao, Jun Liu, Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
Yu-Ting Ruan, Department of Rehabilitation Medicine, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510000, Guangdong Province, China
Jing Zhao, Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Yu-Wen Yang, Li-Ping Chen, Department of Medical Ultrasound, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, Guangdong Province, China
Fei-Fei Liu, Department of Medical Ultrasound, Xiang’an Hospital of Xiamen University, Xiamen 361000, Fujian Province, China
Wang Liao, Department of Neurology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510000, Guangdong Province, China
Author contributions: Xiong Y and Ruan YT contributed to designing this study, collecting samples, carrying out experiments and writing the manuscript; Zhao J, Yang YW, Chen LP and Mai YR contributed to collecting samples and revising the manuscript; Yu Q, Cao ZY, Liu FF and Liao W contributed to analyzing the data and revising the manuscript; Liu J had full access to all of the data in the study, and took responsibility for the integrity of the data and the accuracy of the data analysis; all authors have approved the final article.
Supported by National Natural Science Foundation of China, No. 81870836; Natural Science Foundation of Guangdong Province, China, No. 2020A1515010210; Science and Technology Program of Guangzhou, China, No. 202007030010; and Guangdong Basic and Applied Basic Research Foundation, China, No. 2020A1515110317 and No. 2021A1515010705.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC), Sun Yat-sen University (Approval No. SYSU-IACUC-2019-000005).
Conflict-of-interest statement: All authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Jun Liu, MD, Professor, Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou 510120, Guangdong Province, China. liujun6@mail.sysu.edu.cn
Received: October 11, 2021
Peer-review started: October 11, 2021
First decision: November 17, 2021
Revised: December 15, 2021
Accepted: March 6, 2022
Article in press: March 6, 2022
Published online: March 19, 2022
Processing time: 158 Days and 1.8 Hours
ARTICLE HIGHLIGHTS
Research background
The increasing prevalence of Alzheimer’s disease (AD) in the elderly population has posed a huge financial and medical burden on the society. Effective methods to block the progression of the cognitive deterioration in AD patients are urgently required. As oxidative stress accounts for a pivotal role in the pathological mechanism of neurodegenerative diseases, including AD, anti-oxidative stress treatments may provide a promising therapeutic direction. Recent study had explored the anti-malondialdehyde effect of magnesium in vitro, however the potential anti-oxidative stress damage effect of Magnesium-L-threonate (MgT) still remains to be verified.
Research motivation
This research investigated the suppressive effect of MgT against oxidative stress injury, thus developing a therapeutic reference basis for the future explorations.
Research objectives
This research aimed to determine the neuroprotective effect of MgT against oxidative stress damage and explore the related mechanism which may bring a research foundation for the feasibility of MgT.
Research methods
As the cell and animal models, amyloid β (Aβ)25-35-treated HT22 cells and APPswe/PS1dE9 (APP/PS1) mice were treated with MgT administration. After the MgT administration, cell counting kit-8 detection was applied to analysis the viability of HT22 cells and the Morris Water Maze test was used to record the cognition of APP/PS1 mice. Reactive oxygen species (ROS) production of HT22 cells and cell apoptosis of both models were all quantified by using the flow cytometry assay. The expression of hypoxia-inducible factor (HIF)-1α, NADPH oxidase (NOX) 4, Aβ1-42, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway proteins was quantified by Western blotting.
Research results
MgT effectively suppressed the HT22 cellular injury triggered by Aβ25-35-induced oxidative stress by elevating the viability, blocking the ROS formation and downregulating HIF-1α. MgT significantly ameliorated the impaired cognitive performance of APP/PS1 mouse and inhibited the upregulation of Aβ1-42, NOX4 and HIF-1α protein expression. In addition, MgT obviously suppressed the cell apoptosis, regulated apoptotic-related proteins and upregulated the PI3K/Akt pathway in both models. In future research, further explorations are required to confirm the above-mentioned effects of MgT in more disease models.
Research conclusions
This study demonstrates the protective effect of MgT against oxidative stress injury in Aβ25-35-treated HT22 cells and APP/PS1 mice.
Research perspectives
This study provides a promising therapeutic agent to ameliorate the oxidative stress damage-associated neurodegenerative diseases. More investigations to demonstrate this effect of MgT on other types of Alzheimer’s disease, in vivo models of other neurodegenerative diseases and clinical experiments are required in further research.
