Effects of silver nanoparticles on the interactions of neuron- and glia-like cells: Toxicity, uptake mechanisms, and lysosomal tracking

I. Lun Hsiao, Yi Kong Hsieh, Chun Yu Chuang, Chu Fang Wang, Yuh Jeen Huang

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)


Silver nanoparticles (AgNPs) are commonly used nanomaterials in consumer products. Previous studies focused on its effects on neurons; however, little is known about their effects and uptake mechanisms on glial cells under normal or activated states. Here, ALT astrocyte-like, BV-2 microglia and differentiated N2a neuroblastoma cells were directly or indirectly exposed to 10 nm AgNPs using mono- and co-culture system. A lipopolysaccharide (LPS) was pretreated to activate glial cells before AgNP treatment for mimicking NP exposure under brain inflammation. From mono-culture, ALT took up the most AgNPs and had the lowest cell viability within three cells. Moreover, AgNPs induced H2O2 and NO from ALT/activated ALT and BV-2, respectively. However, AgNPs did not induce cytokines release (IL-6, TNF-α, MCP-1). LPS-activated BV-2 took up more AgNPs than normal BV-2, while the induction of ROS and cytokines from activated cells were diminished. Ca2+-regulated clathrin- and caveolae-independent endocytosis and phagocytosis were involved in the AgNP uptake in ALT, which caused more rapid NP translocation to lysosome than in macropinocytosis and clathrin-dependent endocytosis-involved BV-2. AgNPs directly caused apoptosis and necrosis in N2a cells, while by indirect NP exposure to bottom chamber ALT or BV-2 in Transwell, more apoptotic upper chamber N2a cells were observed. Cell viability of BV-2 also decreased in an ALT–BV-2 co-culturing study. The damaged cells correlated to NP-mediated H2O2 release from ALT or NO from BV-2, which indicates that toxic response of AgNPs to neurons is not direct, but indirectly arises from AgNP-induced soluble factors from other glial cells.

Original languageEnglish
Pages (from-to)1742-1753
Number of pages12
JournalEnvironmental Toxicology
Issue number6
Publication statusPublished - Jun 1 2017
Externally publishedYes


  • central nervous system
  • coculture
  • cytokines
  • reactive oxygen and nitrogen species
  • silver nanoparticles
  • uptake mechanisms

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis


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