Effects of p-Nitrotoluene on Cultured Mesencephalic Neural Stem Cells

抄録

Current risk assessment methods for environmental chemicals are based on adult physiology. However, recent reports have shown an increased incidence of neurodevelopmental disorders which may result from exposure to chemical in utero and during the early postnatal period. We previously showed that exposure of neonates to the environmental chemical p-nitrotoluene caused hyperactivity, accompanied by changes in the expression of the mesencephalic dopamine transporter gene. In this study, we have examined the effects of p-nitrotoluene on cultured neural stem cells isolated from the rat mesencephalon. At embryonic day 15 (E15), these cells stained positive with antibodies against nestin, microtubule-associated proteins (MAPs), and glial fibrillary acidic proteins (GFAPs). The treatment of cultured neurospheres with p-nitrotoluene (1 μM; 72 hr) facilitated differentiation with two distinct morphologies outside the sphere, being neural and glial lineages. Neurospheres could therefore be used as a very simple primary assay for screening environmental chemicals for disruption of developmental programming.