Potential Links between Cytoskeletal Disturbances and Electroneurophysiological Dysfunctions Induced in the Central Nervous System by Inorganic Nanoparticles

Kang, Youjeong; Liu, Jia; Song, Bin; Feng, Xiaochi; Ou, Lingling; Wei, Limin; Li, Xuan; Shao, Longquan

doi:10.1159/000453200

Cited by 21 publications

(8 citation statements)

References 134 publications

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“…This was in significant accordance with the intracellular oxidative stress levels measured by SOD inhibition, as well as with the reactive oxygen species generation. After these assessments, we investigated the modulation of the cell cytoskeleton, as an increase of intracellular ROS could affect the F-actin organization [62]. The cytoskeleton is characterized by a set of filaments (actin microfilaments, microtubules, and intermediate filaments) organized in a network that affects the mechanical properties of cells, as well as their behavior [29].…”

Section: Discussionmentioning

confidence: 99%

Tailoring Cell Morphomechanical Perturbations Through Metal Oxide Nanoparticles

et al. 2019

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The nowadays growing use of nanoparticles (NPs) in commercial products does not match a comprehensive understanding of their potential harmfulness. More in vitro investigations are required to address how the physicochemical properties of NPs guide their engulfment within cells and their intracellular trafficking, fate, and toxicity. These nano-bio interactions have not been extensively addressed yet, especially from a mechanical viewpoint. Cell mechanic is a critical indicator of cell health because it regulates processes like cell migration, tissue integrity, and differentiation via cytoskeleton rearrangements. Here, we investigated in vitro the elasticity perturbation of Caco-2 and A549 cell lines, in terms of Young’s modulus modification induced by SiO 2 NP S and TiO 2 NP S . TiO 2 NPs demonstrated stronger effects on cell elasticity compared to SiO 2 NPs, as they induced significant morphological and morphometric changes in actin network. TiO 2 NP S increased the elasticity in Caco-2 cells, while opposite effects have been observed on A549 cells. These results demonstrate the existence of a correlation between the alteration of cell elasticity and NPs toxicity that depends, in turn, on the NPs physicochemical properties and the specific cell tested.

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Section: Discussionmentioning

confidence: 99%

Tailoring Cell Morphomechanical Perturbations Through Metal Oxide Nanoparticles

et al. 2019

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“…Cytoskeleton organization (e.g. disrupted genes involved in cell matrix, microtubule, actin polymerization, cytokinesis or signal transduction) responses depend on NP and exposure dose (Kang et al 2016;Soenen et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Application of Bayesian networks in determining nanoparticle-induced cellular outcomes using transcriptomics

et al. 2019

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Inroads have been made in our understanding of the risks posed to human health and the environment by nanoparticles (NPs) but this area requires continuous research and monitoring. Machine learning techniques have been applied to nanotoxicology with very encouraging results. This study deals with bridging physicochemical properties of NPs, experimental exposure conditions and in vitro characteristics with biological effects of NPs on a molecular cellular level from transcriptomics studies. The bridging is done by developing and implementing Bayesian Networks (BNs) with or without data preprocessing. The BN structures are derived either automatically or methodologically and compared. Early stage nanotoxicity measurements represent a challenge, not least when attempting to predict adverse outcomes and modeling is critical to understanding the biological effects of exposure to NPs. The preprocessed data-driven BN showed improved performance over automatically structured BN and the BN with unprocessed datasets. The prestructured BN captures inter relationships between NP properties, exposure condition and in vitro characteristics and links those with cellular effects based on statistic correlation findings. Information gain analysis showed that exposure dose, NP and cell line variables were the most influential attributes in predicting the biological effects. The BN methodology proposed in this study successfully predicts a number of toxicologically relevant cellular disrupted biological processes such as cell cycle and proliferation pathways, cell adhesion and extracellular matrix responses, DNA damage and repair mechanisms etc., with a success rate >80%. The model validation from independent data shows a robust and promising methodology for incorporating transcriptomics outcomes in a hazard and, by extension, risk assessment modeling framework by predicting affected cellular functions from experimental conditions.

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“…refs 12 , 13 ). Recently, a few excellent reviews, focused on the potential medical applications of NPs 14 – 16 , have provided a comprehensive picture of the available knowledge about NPs and neuronal ionic channels; some of them also report the effects on action potential firing. Interestingly, both excitatory 17 and inhibitory 18 , 19 effects have been observed.…”

Section: Introductionmentioning

confidence: 99%

SiO2 nanoparticles modulate the electrical activity of neuroendocrine cells without exerting genomic effects

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Antoniotti

et al. 2018

Sci Rep

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Engineered silica nanoparticles (NPs) have attracted increasing interest in several applications, and particularly in the field of nanomedicine, thanks to the high biocompatibility of this material. For their optimal and controlled use, the understanding of the mechanisms elicited by their interaction with the biological target is a prerequisite, especially when dealing with cells particularly vulnerable to environmental stimuli like neurons. Here we have combined different electrophysiological approaches (both at the single cell and at the population level) with a genomic screening in order to analyze, in GT1-7 neuroendocrine cells, the impact of SiO2 NPs (50 ± 3 nm in diameter) on electrical activity and gene expression, providing a detailed analysis of the impact of a nanoparticle on neuronal excitability. We find that 20 µg mL−1 NPs induce depolarization of the membrane potential, with a modulation of the firing of action potentials. Recordings of electrical activity with multielectrode arrays provide further evidence that the NPs evoke a temporary increase in firing frequency, without affecting the functional behavior on a time scale of hours. Finally, NPs incubation up to 24 hours does not induce any change in gene expression.

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Potential Links between Cytoskeletal Disturbances and Electroneurophysiological Dysfunctions Induced in the Central Nervous System by Inorganic Nanoparticles

Cited by 21 publications

References 134 publications

Tailoring Cell Morphomechanical Perturbations Through Metal Oxide Nanoparticles

Tailoring Cell Morphomechanical Perturbations Through Metal Oxide Nanoparticles

Application of Bayesian networks in determining nanoparticle-induced cellular outcomes using transcriptomics

SiO2 nanoparticles modulate the electrical activity of neuroendocrine cells without exerting genomic effects

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