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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

REM (A) and TEM (B) images of neuronal network cultures exposed to 5 μg/cm2 Fe2O3 NPs for 24 hr. In A, particles were detected as agglomerates (large arrows) and as single particles (small arrows); bar = 5 μm. In B, NPs were detected inside cells (arrow); bar = 2 μm.
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f5-ehp-118-1363: REM (A) and TEM (B) images of neuronal network cultures exposed to 5 μg/cm2 Fe2O3 NPs for 24 hr. In A, particles were detected as agglomerates (large arrows) and as single particles (small arrows); bar = 5 μm. In B, NPs were detected inside cells (arrow); bar = 2 μm.

Mentions: Binding of Fe2O3 to the cell surface of neuronal network cells and particle uptake by endocytosis was visible by electron microscopy (Figure 5). In about 1% of investigated cell preparations, we found NPs in what looked like a loose neuropil also containing synapses (Figure 5B). A differentiation of glial cells or the special subtypes of neurons was not possible in TEM.


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)

REM (A) and TEM (B) images of neuronal network cultures exposed to 5 μg/cm2 Fe2O3 NPs for 24 hr. In A, particles were detected as agglomerates (large arrows) and as single particles (small arrows); bar = 5 μm. In B, NPs were detected inside cells (arrow); bar = 2 μm.
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f5-ehp-118-1363: REM (A) and TEM (B) images of neuronal network cultures exposed to 5 μg/cm2 Fe2O3 NPs for 24 hr. In A, particles were detected as agglomerates (large arrows) and as single particles (small arrows); bar = 5 μm. In B, NPs were detected inside cells (arrow); bar = 2 μm.
Mentions: Binding of Fe2O3 to the cell surface of neuronal network cells and particle uptake by endocytosis was visible by electron microscopy (Figure 5). In about 1% of investigated cell preparations, we found NPs in what looked like a loose neuropil also containing synapses (Figure 5B). A differentiation of glial cells or the special subtypes of neurons was not possible in TEM.

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