Quantitative analyses of inhibitory effects of bisphenol a on neural stem-cell migration using a neurosphere assay in vitro

Abstract

The large numbers of environmental chemicals that now exist have made assessing their neurodevelopmental risks challenging. In this study, we quantified neurodevelopmental toxicity of bisphenol A, using a neurosphere assay in vitro. Neurosphere was isolated from rat E16 mesencephalone. A neurosphere assay was carried out in the amine-coated plates. Cells emerged from the neurosphere and migrated along the radial axis from the sphere. The migrating populations comprised cells that were positive for nestin, microtubule-associated proteins, and glial fibrillary acidic protein. Exposure to bisphenol A inhibited cell migration and decreased proliferative cells in dosedependent manner. Quantitative analyses revealed a linear function between the inhibition of migration and the logarithm of bisphenol A concentration (0-100μM); the percent inhibition by 1μM bisphenol A of migration was 35% (p < 0.05). Thus, we showed for first time that bisphenol A inhibited migration as well as proliferation of neural stem cells in vitro and that a neurosphere assay in vitro is very useful to rapidly quantify neurodevelopmental toxicity of environmental chemicals. © 2010 The Pharmaceutical Society of Japan.