AlCl3 exposure regulates neuronal development by modulating DNA modification
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.BACKGROUNDAs the third most abundant element, aluminum is widespread in the environ...
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| Published in | World journal of stem cells Vol. 12; no. 11; pp. 1354 - 1365 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Baishideng Publishing Group Inc
26.11.2020
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| Subjects | |
| Online Access | Get full text |
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| Summary: | 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.BACKGROUNDAs 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.To study the effects of aluminum on epigenetic modification in neural stem cells and neurons.AIMTo study the effects of aluminum on epigenetic modification in neural stem cells and neurons.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.METHODSNeural 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.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.RESULTSAluminum 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.Our findings indicate that aluminum may regulate neuronal development by modulating DNA modifications.CONCLUSIONOur findings indicate that aluminum may regulate neuronal development by modulating DNA modifications. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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). 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. 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 |
| ISSN: | 1948-0210 1948-0210 |
| DOI: | 10.4252/wjsc.v12.i11.1354 |