title: Repulsive Apoptosis During Exposure of Mesencephalic Neural Stem Cells to Silver Nanoparticles in a Neurosphere Assay In Vitro.
abstract: Neurodevelopmental toxicity of silver nanoparticles (AgNPs) remains largely unknown. In this study, we applied a neurosphere assay for neurodevelopmental effects of AgNPs. The neural stem cells were isolated from rat mesencephalon. They were cultured as a sphere. In an assay with coated plates, cells appeared by anchoraging on the dish and then started to migrate along the radial axis from the neurosphere. AgNPs inhibited cell migration in a dose-dependent manner. There was a linear correlation between the inhibition of migration and the logarithm of the particle concentration (1.25-10 μg/ml); the half-maximal inhibitory concentration was 0.41 μg/ml for 16-h exposure. Preceding migrated cells were retarded and/or collapsed by exposure to AgNPs: lower doses of AgNPs (0.31-1.2 μg/ml) caused a 42% retardation for 48 h, while higher doses of AgNPs (2.5-10 μg/ml) collasped migrating cells. Furthermore, collapsed cells were TUNEL-positive and showed a defect in the mitochondrial membrane potential. Thus, we showed the neurodevelopmental toxicity of AgNPs using an in vitro neurosphere assay system.
authors.affiliation: Center for Environmental Risk Research, National Institute for Environmental Studies, Tsukuba 305-8506, Japan. ishidou@nies.go.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Ishido
authors.forename: Eiko
authors.initials: E
authors.lastname: Shimaya
authors.forename: Rumiko
authors.initials: R
authors.lastname: Usu
authors.forename: Yoshika
authors.initials: Y
authors.lastname: Kurokawa
authors.forename: Seishiro
authors.initials: S
authors.lastname: Hirano
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001681:Biological Assay; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008636:Mesencephalon / Q000166:cytology*; D053768:Metal Nanoparticles / Q000633:toxicity*; D058953:Neural Stem Cells / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D017208:Rats, Wistar; D012834:Silver / Q000633:toxicity*
chemical_list: D012834:Silver