Limits...
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.

Show MeSH

Related in: MedlinePlus

Changes in four general activity parameters of neuronal networks after exposure to Fe2O3 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
getmorefigures.php?uid=PMC2957913&req=5

f4-ehp-118-1363: Changes in four general activity parameters of neuronal networks after exposure to Fe2O3 NPs. (A) SR. (B) BR. (C) Burst duration. (D) Spikes in burst.*p < 0.05. **p < 0.01. #p < 0.001.

Mentions: We tested Fe2O3 NPs for neurotoxic potential in concentrations of 0.1–100 μg/cm2 (n = 16 per treatment). These NPs caused less pronounced changes in the cortical activity network patterns than did CB NPs. The general activity showed a steady reduction with rising Fe2O3 concentrations, with a maximum decline in SR and BR to 71.0 ± 3.1%, and 76 ± 3.7%, respectively, at 100 μg/cm2 (the highest concentration tested) (Figure 4). At a concentration of 0.5 μg/cm2, Fe2O3 induced a significant decrease in activity. We calculated the EC10, EC50, and EC90 values for the SR as 0.025, 6.6, and 1,760 μg/cm2, respectively (Table 2). This effect on SR was accompanied by changes in the burst structure (specifically, a decrease in the number of spikes in burst to 88.1 ± 2.4%) (Figure 4) and by a reduction in synchronicity and oscillatory behavior [see Supplemental Material, Figures 6 and 7 (doi:10.1289/ehp.0901661)]. However, even at the highest concentration tested, all neurons in the network remained actively bursting. In 16 of the 31 activity parameters, Fe2O3 induced significant changes.


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)

Changes in four general activity parameters of neuronal networks after exposure to Fe2O3 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

f4-ehp-118-1363: Changes in four general activity parameters of neuronal networks after exposure to Fe2O3 NPs. (A) SR. (B) BR. (C) Burst duration. (D) Spikes in burst.*p < 0.05. **p < 0.01. #p < 0.001.
Mentions: We tested Fe2O3 NPs for neurotoxic potential in concentrations of 0.1–100 μg/cm2 (n = 16 per treatment). These NPs caused less pronounced changes in the cortical activity network patterns than did CB NPs. The general activity showed a steady reduction with rising Fe2O3 concentrations, with a maximum decline in SR and BR to 71.0 ± 3.1%, and 76 ± 3.7%, respectively, at 100 μg/cm2 (the highest concentration tested) (Figure 4). At a concentration of 0.5 μg/cm2, Fe2O3 induced a significant decrease in activity. We calculated the EC10, EC50, and EC90 values for the SR as 0.025, 6.6, and 1,760 μg/cm2, respectively (Table 2). This effect on SR was accompanied by changes in the burst structure (specifically, a decrease in the number of spikes in burst to 88.1 ± 2.4%) (Figure 4) and by a reduction in synchronicity and oscillatory behavior [see Supplemental Material, Figures 6 and 7 (doi:10.1289/ehp.0901661)]. However, even at the highest concentration tested, all neurons in the network remained actively bursting. In 16 of the 31 activity parameters, Fe2O3 induced significant changes.

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