title: Interaction of SiO2 nanoparticles with neuronal cells: Ionic mechanisms involved in the perturbation of calcium homeostasis.
abstract: SiO2 nanoparticles (NPs), in addition to their widespread utilization in consumer goods, are also being engineered for clinical use. They are considered to exert low toxicity both in vivo and in vitro, but the mechanisms 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 nervous system: silica NPs are good candidates for nanoneuromedicine applications. Here, by using two neuronal cell lines (GT1-7 and GN11 cells), derived from gonadotropin hormone releasing hormone (GnRH) neurons, we describe the mechanisms involved in the perturbation of calcium signaling, a key controller of neuronal function. At the non-toxic dose of 20μgmL(-1), 50nm SiO2 NPs induce long lasting but reversible calcium signals, that in most cases show a complex oscillatory behavior. Using fluorescent NPs, we show that these signals do not depend on NPs internalization, are totally ascribable to calcium influx and are dependent in a complex way from size and surface charge. We provide evidence of the involvement of voltage-dependent and transient receptor potential-vanilloid 4 (TRPV4) channels.
authors.affiliation: Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Torino, Italy; NIS Centre, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gilardino
authors.affiliation: Department of Chemistry, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy; NIS Centre, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Catalano
authors.affiliation: Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Torino, Italy; NIS Centre, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy.
authors.forename: Federico Alessandro
authors.initials: FA
authors.lastname: Ruffinatti
authors.affiliation: Department of Chemistry, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy; NIS Centre, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Alberto
authors.affiliation: Department of Cellular and Molecular Medicine, Laboratory of Ion Channel Research KU Leuven, Leuven, Belgium.
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.affiliation: Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Torino, Italy; NIS Centre, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Antoniotti
authors.affiliation: Department of Chemistry, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy; NIS Centre, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy. Electronic address: gianmario.martra@unito.it.
authors.forename: Gianmario
authors.initials: G
authors.lastname: Martra
authors.affiliation: Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Torino, Italy; NIS Centre, University of Torino, Via Pietro Giuria 7, 10125 Torino, Italy; Neuroscience Institute of Torino, University of Torino, Torino, Italy. Electronic address: davide.lovisolo@unito.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Lovisolo
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D007477:Ions / Q000378:metabolism; D051379:Mice; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010316:Particle Size; D012822:Silicon Dioxide / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D007477:Ions; D050916:TRPV Cation Channels; C486576:Trpv4 protein, mouse; D012822:Silicon Dioxide; D002118:Calcium
keywords: Calcium signaling/homeostasis; Neurons; Silica nanoparticles; TRPV4 channels; Voltage dependent channels