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Nanoparticles induce changes of the electrical activity of neuronal networks on microelectrode array neurochips.

Gramowski A, Flossdorf J, Bhattacharya K, Jonas L, Lantow M, Rahman Q, Schiffmann D, Weiss DG, Dopp E - Environ. Health Perspect. (2010)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biological Sciences, Cell Biology and Biosystems Technology, University of Rostock, Rostock, Germany.

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.

Objectives/methods: 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.

Conclusion: 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.

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Related in: MedlinePlus

ROS levels after exposure of neuronal networks to different concentrations of CB, Fe2O3, or TiO2 NPs for 24 hr. (A) Cell autofluorescence (“Blank”) and the changes in fluorescence intensity and peak distribution of rhodamine 123 analyzed by flow cytometry (DHR assay), in control cells and in cells exposed to NPs. (B) ROS formation in neuronal cells after exposure to different concentrations (0.5–10 μg/cm2) of NPs. Values shown are the mean ± SD of experiment/control (E/C) data from three independent experiments (and preparations) performed in triplicate.#p < 0.001.
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f3-ehp-118-1363: ROS levels after exposure of neuronal networks to different concentrations of CB, Fe2O3, or TiO2 NPs for 24 hr. (A) Cell autofluorescence (“Blank”) and the changes in fluorescence intensity and peak distribution of rhodamine 123 analyzed by flow cytometry (DHR assay), in control cells and in cells exposed to NPs. (B) ROS formation in neuronal cells after exposure to different concentrations (0.5–10 μg/cm2) of NPs. Values shown are the mean ± SD of experiment/control (E/C) data from three independent experiments (and preparations) performed in triplicate.#p < 0.001.

Mentions: We investigated the effects of the different NPs at concentrations of 0.5, 5, and 10 μg/cm2 after 24-hr exposure on the formation of ROS (Figure 3). Results show that exposure to CB NPs did not induce changes in the ROS level in neuronal networks.


Nanoparticles induce changes of the electrical activity of neuronal networks on microelectrode array neurochips.

Gramowski A, Flossdorf J, Bhattacharya K, Jonas L, Lantow M, Rahman Q, Schiffmann D, Weiss DG, Dopp E - Environ. Health Perspect. (2010)

ROS levels after exposure of neuronal networks to different concentrations of CB, Fe2O3, or TiO2 NPs for 24 hr. (A) Cell autofluorescence (“Blank”) and the changes in fluorescence intensity and peak distribution of rhodamine 123 analyzed by flow cytometry (DHR assay), in control cells and in cells exposed to NPs. (B) ROS formation in neuronal cells after exposure to different concentrations (0.5–10 μg/cm2) of NPs. Values shown are the mean ± SD of experiment/control (E/C) data from three independent experiments (and preparations) performed in triplicate.#p < 0.001.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2957913&req=5

f3-ehp-118-1363: ROS levels after exposure of neuronal networks to different concentrations of CB, Fe2O3, or TiO2 NPs for 24 hr. (A) Cell autofluorescence (“Blank”) and the changes in fluorescence intensity and peak distribution of rhodamine 123 analyzed by flow cytometry (DHR assay), in control cells and in cells exposed to NPs. (B) ROS formation in neuronal cells after exposure to different concentrations (0.5–10 μg/cm2) of NPs. Values shown are the mean ± SD of experiment/control (E/C) data from three independent experiments (and preparations) performed in triplicate.#p < 0.001.
Mentions: We investigated the effects of the different NPs at concentrations of 0.5, 5, and 10 μg/cm2 after 24-hr exposure on the formation of ROS (Figure 3). Results show that exposure to CB NPs did not induce changes in the ROS level in neuronal networks.

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biological Sciences, Cell Biology and Biosystems Technology, University of Rostock, Rostock, Germany.

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.

Objectives/methods: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus