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

Indian Journal of Pharmaceutical Education and Research

  • Wenyan Ying1College of Sports and Health, Shandong Sport University, Jinan, CHINA., 2Key Laboratory of Biomedical Engineering and Technology of Shandong High School, Qilu Medical University, Zibo, CHINA.
  • Tongbing Qi1College of Sports and Health, Shandong Sport University, Jinan, CHINA., 2Key Laboratory of Biomedical Engineering and Technology of Shandong High School, Qilu Medical University, Zibo, CHINA.
  • Dongzi Shi1College of Sports and Health, Shandong Sport University, Jinan, CHINA., 2Key Laboratory of Biomedical Engineering and Technology of Shandong High School, Qilu Medical University, Zibo, CHINA.
  • Jing Zhang2Key Laboratory of Biomedical Engineering and Technology of Shandong High School, Qilu Medical University, Zibo, CHINA.
  • Ganghui Ye2Key Laboratory of Biomedical Engineering and Technology of Shandong High School, Qilu Medical University, Zibo, CHINA.
  • Xuewen Tian1College of Sports and Health, Shandong Sport University, Jinan, CHINA.
  • Qinglu Wang1College of Sports and Health, Shandong Sport University, Jinan, CHINA., 2Key Laboratory of Biomedical Engineering and Technology of Shandong High School, Qilu Medical University, Zibo, CHINA.

Volume 57 Issue 1 Pages 155-160

DOI: 10.5530/001954641252

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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