Transcriptomic insight into cadmium-induced neurotoxicity in embryonic neural stem/progenitor cells. (February 2020)

• Record Type: Journal Article
• Authors: Deng, Ping; Ma, Qinlong; Xi, Yu; Yang, Lingling; Lin, Min; Yu, Zhengping; Chen, Chunhai; Zhou, Zhou
• Is Part Of: Toxicology in vitro. Volume 62(2020)
• Publication Date: 2020-02
• Subjects: Cadmium -- Neurotoxicity -- Embryonic neural stem/progenitor cells; NSPCs neural stem/progenitor cells -- mRNA-seq mRNA transcriptome sequencing -- P53 tumour protein 53 -- PI3K-AKT phosphatidylinositol 3 kinase (PI3K) - protein kinase B (AKT) -- MAPK mitogen-activated protein kinase -- NF-kappa B nuclear factor kappa B -- PCR polymerase chain reaction -- logFC log2-fold change between two experimental conditions; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2019.104686
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Cadmium exposure has raised great public concern. Extensive studies have revealed the neurotoxic effects of cadmium exposure during brain development. However, more evidence is still needed to reach a consistent conclusion and uncover the underlying mechanisms. Here, we used primary mouse embryonic neural stem/progenitor cells (NSPCs) as a cell model and exposed the cells to 0, 1, 2 or 4 μM cadmium. High-throughput mRNA-seq technology was used to explore the global transcriptome changes in NSPCs after exposure to 2 μM cadmium. We found that cadmium exposure remarkably influenced the expression of genes involved in cell growth, proliferation, cell cycle and survival. Pathway-Act-Network analysis revealed that these altered genes were targeted to the P53, PI3K-AKT, MAPK, calcium, and NF-kappa B signaling pathways. In vitro experiments using cultured NSPCs verified that cadmium exposure reduced cell viability, proliferation, neurosphere formation and caused cell cycle arrest at low concentrations (≤ 2 μM), while induced cell apoptosis at high concentrations (≥ 4 μM). Real-time PCR results confirmed the concentration-dependent effects of cadmium exposure on the expression of critical genes in the above signaling pathways. Together, our results provide transcriptomic insight into cadmium-induced developmental neurotoxic effects and the underlying mechanisms. Highlights: Cadmium exposure influenced genes involved in cell growth, proliferation, cell cycle and survival. Cadmium-altered genes were targeted to the P53, PI3K-AKT, MAPK and NF-kappa B signaling pathways. Cadmium exposure reduced NSPC viability, proliferation and neurosphere formation at low concentrations (≤ 2 μM). Cadmium exposure induced NSPC apoptosis at high concentrations (≥ 4 μM).