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IJPER · Lens · Methylmercury, Mn2+ and Pb2+ Exposure Promotes Premature Proliferation/Differentiation of Human Neural Stem Cells in Different Ways

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Article · Volume 57, Issue 1 · pp. 155–160

Methylmercury, Mn2+ and Pb2+ Exposure Promotes Premature Proliferation/Differentiation of Human Neural Stem Cells in Different Ways

Wenyan Ying1,2, Tongbing Qi1,2, Dongzi Shi1,2, Jing Zhang2, Ganghui Ye2, Xuewen Tian1, Qinglu Wang1,2

  1. 1College of Sports and Health, Shandong Sport University, Jinan, CHINA.
  2. 2Key Laboratory of Biomedical Engineering and Technology of Shandong High School, Qilu Medical University, Zibo, CHINA.

Abstract

Background: Methylmercury (MeHg), manganese ions (Mn2+), and lead ions (Pb2+) are ubiquitous environmental pollutants and may be neurotoxic especially during fetal development. We decided to explore the toxic mechanisms of MeHg (organic heavy metals), Mn2+ (inorganic heavy metals) and Mn2+ on the proliferation and differentiation of human neural stem cells (hNSCs).Materials and Methods: The proliferation and apoptosis of hNSCs were analyzed via CCK-8 method and flow cytometry under MeHg, Mn2+ and Pb2+, respectively. RNA-seq was used for analyzing proliferation/differentiation mechanism of MeHg, Mn2+ and Pb2+ stressing hNSCs.Results: Our experiment found that when hNSCs were exposed to below 0.5 nM MeHg, 5μM Mn2+ and 10 μM Pb2+, cell proliferation and differentiation were promoted. Apoptosis rates increased significantly when hNSCS were exposed to exceed 0.5 nM MeHg, 5μM Mn2+ and 10 μM Pb2+. RNA-seq results showed that metal ions altered the genes expression level and signaling pathways of hNSC differentiation and proliferation, but the regulatory mechanisms of MeHg, Mn2+ and Pb2+ were different.Conclusion: Our findings indicated that very low-dose metal exposure may deplete hNSC pool by making prematurely differentiated neurons increase, which may be the real cause of long-term nervous system disruption in adulthood, rather than higher metal doses will cause more direct toxicity during infant development.

Keywords: Methylmercury; Manganese ion; Lead ion; Neural stem cells; Cell differentiation

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