Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Nov 26, 2020; 12(11): 1354-1365
Published online Nov 26, 2020. doi: 10.4252/wjsc.v12.i11.1354
AlCl3 exposure regulates neuronal development by modulating DNA modification
Xue-Jun Cheng, Fu-Lai Guan, Qian Li, Gong Dai, Hai-Feng Li, Xue-Kun Li
Xue-Jun Cheng, Qian Li, Hai-Feng Li, Xue-Kun Li, The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, Zhejiang Province, China
Xue-Jun Cheng, Qian Li, Xue-Kun Li, The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, Zhejiang Province, China
Xue-Jun Cheng, Qian Li, Hai-Feng Li, Xue-Kun Li, National Clinical Research Center for Child Health, Hangzhou 310052, Zhejiang Province, China
Fu-Lai Guan, Gong Dai, School of Basic Medicine, Weifang Medical University, Weifang 261053, Shandong Province, China
Author contributions: Li XK designed the study; Cheng XJ performed the isolation and culture of adult neural stem cells, proliferation and differentiation assays, qRT-PCR, Western blot, and DNA dot-blots; Guan FL and Dai G performed the quantification analysis of immunofluorescence staining; Li Q performed neuronal culture and Sholl analysis; Li XK and Li HF wrote the manuscript; all authors reviewed and approved the final manuscript. Xue-Jun Cheng and Fu-Lai Guan contributed equally to this study.
Supported by the National Key Research and Development Program of China during the 13th Five-Year Plan, No. 2016YFC1306205; the Provincial Key Disciplines of Zhejiang Traditional Chinese Medicine (Combination of Traditional Chinese and Western Medicine), No. 2017-XK-A41 (to Li HF); and the National Natural Science Foundation of China, Nos. 31771395 and 31571518 (to Li XK).
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the Institute of the Translational Medicine, School of Medicine, Zhejiang University.
Institutional animal care and use committee statement: All animal experiments conformed to The Institutional Animal Care and Use Committee (School of Medicine, Zhejiang University, China; protocol No. ZJU2015-136-01).
Conflict-of-interest statement: Dr. Li XK got the financial support from the National Natural Science Foundation of China.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Xue-Kun Li, PhD, Professor, The Institute of Translational Medicine, School of Medicine, Zhejiang University, No. 268 Kaixuan Road, Central North Building Room 440, Huajiachi Campus, Hangzhou 310029, Zhejiang Province, China. xuekun_li@zju.edu.cn
Received: March 28, 2020
Peer-review started: March 30, 2020
First decision: July 5, 2020
Revised: July 7, 2020
Accepted: September 8, 2020
Article in press: September 8, 2020
Published online: November 26, 2020
Processing time: 243 Days and 5.6 Hours
Abstract
BACKGROUND

As the third most abundant element, aluminum is widespread in the environment. Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive function.

AIM

To study the effects of aluminum on epigenetic modification in neural stem cells and neurons.

METHODS

Neural stem cells were isolated from the forebrain of adult mice. Neurons were isolated from the hippocampi tissues of embryonic day 16-18 mice. AlCl3 at 100 and 200 μmol/L was applied to stem cells and neurons.

RESULTS

Aluminum altered the differentiation of adult neural stem cells and caused apoptosis of newborn neurons while having no significant effects on the proliferation of neural stem cells. Aluminum application also significantly inhibited the dendritic development of hippocampal neurons. Mechanistically, aluminum exposure significantly affected the levels of DNA 5-hydroxy-methylcytosine, 5-methylcytosine, and N6-methyladenine in stem cells and neurons.

CONCLUSION

Our findings indicate that aluminum may regulate neuronal development by modulating DNA modifications.

Keywords: Aluminum; DNA demethylation; 5-hydroxymethylcytosine; Neural stem cells; Neuron; Neuronal development

Core Tip: Although the neurotoxic effects of aluminum have been known, it is still unclear regarding the effects of aluminum on epigenetic modifications in the context of neuronal development. Our present study revealed that aluminum exerted the neurotoxic effects including promoting cell death by regulating DNA modifications. These results highlight the crosstalk between the environment and epigenetics, and subsequent phenotypes. Our findings emphasize the importance of protecting the environment and improving food safety.