Interaction of SiO2 nanoparticles with neuronal cells: ionic mechanisms involved in the perturbation of calcium homeostasis

SiO2nanoparticles (NPs), in addition to their widespread utilization in consumer goods, are also beingengineered for clinical use. They are considered to exert low toxicity both in vivo and in vitro, but themechanisms involved in the cellular responses activated by these nanoobjects, even at non-toxic doses,have not been characterized in detail. This is of particular relevance for their interaction with the nervoussystem: silica NPs are good candidates for nanoneuromedicine applications. Here, by using two neuronalcell lines (GT1–7 and GN11 cells), derived from gonadotropin hormone releasing hormone (GnRH) neu-rons, we describe the mechanisms involved in the perturbation of calcium signaling, a key controller ofneuronal function. At the non-toxic dose of 20 g mL−1, 50 nm SiO2NPs induce long lasting but reversiblecalcium signals, that in most cases show a complex oscillatory behavior. Using fluorescent NPs, we showthat these signals do not depend on NPs internalization, are totally ascribable to calcium influx and aredependent in a complex way from size and surface charge. We provide evidence of the involvement ofvoltage-dependent and transient receptor potential-vanilloid 4 (TRPV4) channels.