Interaction of Spherical Silica Nanoparticles with Neuronal Cells: Size-Dependent Toxicity and Perturbation of Calcium Homeostasis

The effects of Stober silica nanoparticles on neuronal survival, proliferation, and on the underlying perturbations in calcium homeostasis are investigated on the well-differentiated neuronal cell line GT1-7. The responses to nanoparticles 50 and 200 nm in diameter are compared. The 50-nm silica affects neuronal survival/proliferation in a dose-dependent way, by stimulating apoptotic processes. In contrast, 200-nm silica does not show any toxic effects even at relatively high concentrations (292 mu g mL(-1)). To identify the mechanisms underlying these effects, the changes in intracellular calcium concentration elicited by acute and chronic administration of the two silica nanoparticles are analyzed. The 50-nm silica nanoparticles at toxic concentrations generate huge and long-lasting increases in intracellular calcium, whereas 200-nm silica only induces transient signals of much lower amplitude. These findings provide the first evidence that silica nanoparticles can induce toxic effects on neuronal cells in a size-dependent way, and that these effects are related to the degree of perturbation of calcium homeostasis.