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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

Concentration-dependent changes in four general activity parameters of neuronal networks after exposure to CB NPs. (A) SR. (B) BR. (C) Burst duration. (D) Spikes in burst.*p < 0.05. **p < 0.01. #p < 0.001.
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f1-ehp-118-1363: Concentration-dependent changes in four general activity parameters of neuronal networks after exposure to CB NPs. (A) SR. (B) BR. (C) Burst duration. (D) Spikes in burst.*p < 0.05. **p < 0.01. #p < 0.001.

Mentions: We tested CB in a concentration range of 0.001–300 μg/cm2 (n = 8). The high interculture repeatability of the electrophysiological activity response induced by the three NPs is demonstrated in Supplemental Material, Figure 3 (doi:10.1289/ehp.0901661). CB induced biphasic concentration-dependent activity changes in the electrical activity of cortical networks. At low concentrations (0.03–100 μg/cm2), CB evoked a reduction of the general activity (phase 1). This initial activity drop was followed by an increase of the cortical network SR activity at higher CB concentrations (10–300 μg/cm2) (phase 2; Figure 1). In phase 1 the significant decrease in the general activity started at 0.03 μg/cm2 SR, 92.0 ± 1.3%; BR, 93.9 ± 1.4%). We observed a maximum decrease in the general activity at 30 μg/cm2 (SR, 67.2 ± 4.3%; BR, 66.1 ± 4.4%). To determine the EC50, we fitted the dose–response curves to the maximum inducible effect of the NPs. The initial value was set to 100% and the final value was not fixed. Fitted EC10, EC50, and EC90 values for SR in this activity decline (phase 1) were 0.001, 0.915, and 851 μg/cm2, respectively (Table 2). The Hill coefficient for the dose–response curve was 0.32 for the phase 1 slope. During phase 1, activity changes decreased with rising CB concentrations beginning at 10 μg/cm2, which is reflected by an increasing coefficient of variation (CV) averaged over the network (CVnet) for the BR (174.0 ± 24.1%; see Supplemental Material, Figures 4 and 5). These changes were accompanied by a decomposition of the network oscillation at 20 μg/cm2 and upward, which is reflected by the increasing CV averaged over time (CVtime) for the BR (203.0 ± 26.3%). The number of bursting units remained unaltered.


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)

Concentration-dependent changes in four general activity parameters of neuronal networks after exposure to CB NPs. (A) SR. (B) BR. (C) Burst duration. (D) Spikes in burst.*p < 0.05. **p < 0.01. #p < 0.001.
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f1-ehp-118-1363: Concentration-dependent changes in four general activity parameters of neuronal networks after exposure to CB NPs. (A) SR. (B) BR. (C) Burst duration. (D) Spikes in burst.*p < 0.05. **p < 0.01. #p < 0.001.
Mentions: We tested CB in a concentration range of 0.001–300 μg/cm2 (n = 8). The high interculture repeatability of the electrophysiological activity response induced by the three NPs is demonstrated in Supplemental Material, Figure 3 (doi:10.1289/ehp.0901661). CB induced biphasic concentration-dependent activity changes in the electrical activity of cortical networks. At low concentrations (0.03–100 μg/cm2), CB evoked a reduction of the general activity (phase 1). This initial activity drop was followed by an increase of the cortical network SR activity at higher CB concentrations (10–300 μg/cm2) (phase 2; Figure 1). In phase 1 the significant decrease in the general activity started at 0.03 μg/cm2 SR, 92.0 ± 1.3%; BR, 93.9 ± 1.4%). We observed a maximum decrease in the general activity at 30 μg/cm2 (SR, 67.2 ± 4.3%; BR, 66.1 ± 4.4%). To determine the EC50, we fitted the dose–response curves to the maximum inducible effect of the NPs. The initial value was set to 100% and the final value was not fixed. Fitted EC10, EC50, and EC90 values for SR in this activity decline (phase 1) were 0.001, 0.915, and 851 μg/cm2, respectively (Table 2). The Hill coefficient for the dose–response curve was 0.32 for the phase 1 slope. During phase 1, activity changes decreased with rising CB concentrations beginning at 10 μg/cm2, which is reflected by an increasing coefficient of variation (CV) averaged over the network (CVnet) for the BR (174.0 ± 24.1%; see Supplemental Material, Figures 4 and 5). These changes were accompanied by a decomposition of the network oscillation at 20 μg/cm2 and upward, which is reflected by the increasing CV averaged over time (CVtime) for the BR (203.0 ± 26.3%). The number of bursting units remained unaltered.

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