title: Nanoparticles induce changes of the electrical activity of neuronal networks on microelectrode array neurochips.
abstract: BACKGROUND
  Nanomaterials are extensively used in industry and daily life, but little is known about possible health effects. An intensified research regarding toxicity of nanomaterials is urgently needed. Several studies have demonstrated that nanoparticles (NPs; diameter < 100 nm) can be transported to the central nervous system; however, interference of NPs with the electrical activity of neurons has not yet been shown.
  
  
  OBJECTIVE
  We investigated the acute electrophysiological effects of carbon black (CB), hematite (Fe2O3), and titanium dioxide (TiO2) NPs in primary murine cortical networks on microelectrode array (MEA) neurochips. Uptake of NPs was studied by transmission electron microscopy (TEM), and intracellular formation of reactive oxygen species (ROS) was studied by flow cytometry.
  
  
  RESULTS
  The multiparametric assessment of electrical activity changes caused by the NPs revealed an NP-specific and concentration-dependent inhibition of the firing patterns. The number of action potentials and the frequency of their patterns (spike and burst rates) showed a significant particle-dependent decrease and significant differences in potency. Further, we detected the uptake of CB, Fe2O3, and TiO2 into glial cells and neurons by TEM. Additionally, 24 hr exposure to TiO2 NPs caused intracellular formation of ROS in neuronal and glial cells, whereas exposure to CB and Fe2O3 NPs up to a concentration of 10 µg/cm2 did not induce significant changes in free radical levels.
  
  
  CONCLUSIONS
  NPs at low particle concentrations are able to exhibit a neurotoxic effect by disturbing the electrical activity of neuronal networks, but the underlying mechanisms depend on the particle type.
authors.affiliation: Institute of Biological Sciences, Cell Biology and Biosystems Technology, University of Rostock, Rostock, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gramowski
authors.forename: Juliane
authors.initials: J
authors.lastname: Flossdorf
authors.forename: Kunal
authors.initials: K
authors.lastname: Bhattacharya
authors.forename: Ludwig
authors.initials: L
authors.lastname: Jonas
authors.forename: Margareta
authors.initials: M
authors.lastname: Lantow
authors.forename: Qamar
authors.initials: Q
authors.lastname: Rahman
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schiffmann
authors.forename: Dieter G
authors.initials: DG
authors.lastname: Weiss
authors.forename: Elke
authors.initials: E
authors.lastname: Dopp
mesh_terms: D000200:Action Potentials; D000818:Animals; D051379:Mice; D008839:Microelectrodes; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D009415:Nerve Net
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