Nanoparticles Induce Changes of the Electrical Activity of Neuronal Networks on Microelectrode Array Neurochips

Abstract

BackgroundNanomaterials 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.Objectives/methodsWe 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.ResultsThe 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.ConclusionNPs 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.

Nanoparticle Technology as a Double-Edged Sword: Cytotoxic, Genotoxic and Epigenetic Effects on Living Cells

“…Nasal mucosa cells Cytotoxic, genotoxic and pro-inflammatory effects [77] Hepatocytes Inflammatory and genotoxic effects [56] Renal cells Cytotoxicity [78] Neurons Neurotoxic effect by disturbing the electrical activity of neuronal networks [7] Lung epithelial cells Cytotoxicity [79] Carbon black nanoparticles (CB-NPs) Lymphocytes Induction of chromosomal aberrations [80] Hepatocytes Hepatotoxicity [81] Neurons Dopaminergic neurons damage pathways [82] Lung epithelial cells Toxicity and inflammatory response. [83] Lymphocytes Cytotoxicity and genotoxicity [84] Silica nanoparticles (SiO 2 ) Fibroblast Cytotoxicity [25] Hepatocytes Genotoxicity, carcinogenicity, hepatotoxicity and inflammation [48,85] Renal cells Induction of oxidative stress and cytotoxicity [86] Neurons Neurotoxicity [7] Lung epithelial cells Genotoxicity, mutagenicity and carcinogenicity [87,88] Lymphocytes Induction of oxidative stress and reduction of immune capacity, Genotoxicity [27,80] Titanium dioxide nanoparticles (TiO 2 )…”

“…[83] Lymphocytes Cytotoxicity and genotoxicity [84] Silica nanoparticles (SiO 2 ) Fibroblast Cytotoxicity [25] Hepatocytes Genotoxicity, carcinogenicity, hepatotoxicity and inflammation [48,85] Renal cells Induction of oxidative stress and cytotoxicity [86] Neurons Neurotoxicity [7] Lung epithelial cells Genotoxicity, mutagenicity and carcinogenicity [87,88] Lymphocytes Induction of oxidative stress and reduction of immune capacity, Genotoxicity [27,80] Titanium dioxide nanoparticles (TiO 2 )…”

“…Here, we resume current information on negative effects of NPs especially including their toxicity (Figure 1) [5][6][7][8][9][10][11][12][13].…”

Sub-toxic concentrations of nano-ZnO and nano-TiO₂ suppress neurite outgrowth in differentiated PC12 cells

“…Nasal exposure of airborne nano-ZnO or nano-TiO 2 in rodents results in their translocations into the brain (Kao et al, 2012b;Wang et al, 2008), and several groups have reported the effects of these nanomaterials on neuronal viability or neuronal excitability in vitro (Gramowski et al, 2010;Valdiglesias et al, 2013aValdiglesias et al, , 2013bLiu et al, 2010;Long et al, 2007;Jeng and Swanson, 2006). However, it is still unclear whether these nanomaterials affect the differentiation and development of neurons.…”

Assessing the axonal translocation of CeO2 and SiO2 nanoparticles in the sciatic nerve fibers of the frog: an ex vivo electrophysiological study

“…6 During the past several years, there have been numerous toxicological investigations of airborne NPs and their impact on occupational health and the environment. [7][8][9] Experimental models have provided clear evidence that NPs can not only translocate to organs after inhalation, [10][11][12] but can also cause disruption of the blood-brain barrier through different administration routes, including the intravenous, the intraperitoneal, and the intracerebral route. 13,14 Inhaled NPs either translocate directly into the brain or exit the lungs and enter the circulation as shown in rat experiments.…”