Cheng Xue-Jun, Guan Fu-Lai, Li Qian, Dai Gong, Li Hai-Feng, Li Xue-Kun
The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, Zhejiang Province, China.
School of Basic Medicine, Weifang Medical University, Weifang 261053, Shandong Province, China.
World J Stem Cells. 2020 Nov 26;12(11):1354-1365. doi: 10.4252/wjsc.v12.i11.1354.
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.
To 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. AlCl 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 N-methyladenine in stem cells and neurons.
Our findings indicate that aluminum may regulate neuronal development by modulating DNA modifications.
铝作为第三丰富的元素，在环境中广泛存在。先前的研究表明，铝具有神经毒性作用，其暴露会损害神经元发育和认知功能。
研究铝对神经干细胞和神经元表观遗传修饰的影响。
从成年小鼠前脑分离神经干细胞。从胚胎第16 - 18天小鼠的海马组织中分离神经元。将100和200μmol/L的氯化铝应用于干细胞和神经元。
铝改变了成年神经干细胞的分化，导致新生神经元凋亡，而对神经干细胞的增殖没有显著影响。应用铝还显著抑制了海马神经元的树突发育。从机制上讲，铝暴露显著影响干细胞和神经元中DNA 5 - 羟甲基胞嘧啶、5 - 甲基胞嘧啶和N - 甲基腺嘌呤的水平。
我们的研究结果表明，铝可能通过调节DNA修饰来调控神经元发育。
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