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Magnetite-Amyloid-β deteriorates activity and functional organization in an in vitro model for Alzheimer's disease.

Teller S, Tahirbegi IB, Mir M, Samitier J, Soriano J - Sci Rep (2015)

Bottom Line: Recent studies have shown that other agents, in particular magnetite, can also play a pivotal role.Our work suggests that magnetite nanoparticles have a more prominent role in AD than previously thought, and may bring new insights in the understanding of the damaging action of magnetite-amyloid-β complex.Our experimental system also offers new interesting perspectives to explore key biochemical players in neurological disorders through a controlled, model system manner.

View Article: PubMed Central - PubMed

Affiliation: Departament d'Estructura i Constituents de la Matèria, Universitat de Barcelona, Barcelona, E-08028, Spain.

ABSTRACT
The understanding of the key mechanisms behind human brain deterioration in Alzheimer' disease (AD) is a highly active field of research. The most widespread hypothesis considers a cascade of events initiated by amyloid-β peptide fibrils that ultimately lead to the formation of the lethal amyloid plaques. Recent studies have shown that other agents, in particular magnetite, can also play a pivotal role. To shed light on the action of magnetite and amyloid-β in the deterioration of neuronal circuits, we investigated their capacity to alter spontaneous activity patterns in cultured neuronal networks. Using a versatile experimental platform that allows the parallel monitoring of several cultures, the activity in controls was compared with the one in cultures dosed with magnetite, amyloid-β and magnetite-amyloid-β complex. A prominent degradation in spontaneous activity was observed solely when amyloid-β and magnetite acted together. Our work suggests that magnetite nanoparticles have a more prominent role in AD than previously thought, and may bring new insights in the understanding of the damaging action of magnetite-amyloid-β complex. Our experimental system also offers new interesting perspectives to explore key biochemical players in neurological disorders through a controlled, model system manner.

No MeSH data available.


Related in: MedlinePlus

Experiments and data acquisition.(A) Sketch of the experimental setup and procedure. A pierced PDMS layer was attached to a glass coverslip to shape a 2 × 2 grid of cavities, each 3.5 mm in diameter and 4 mm deep. Neurons were plated on these cavities forming independent, mm-sized neuronal networks, and cultured in identical conditions. For measurements, one of the cavities was left as control, while the others were dosed with specific chemical agents. (B) Left: Bright field image of a typical preparation at day in vitro 8, showing the 4 cavities containing the neuronal networks. Dark circular objects are aggregates of neurons (clusters) connected to one another through bundles of neurites. Right: Fluorescence image of the bottom-right culture. Firing clusters appear as bright spots on the images. (C) Representative fluorescence traces of the 4 clusters highlighted in (B), and along 15 min of recording. The yellow boxes illustrate different combinations of co-activations. Clusters #1 and #2 always fire together and shape a strong, persistent community.
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f1: Experiments and data acquisition.(A) Sketch of the experimental setup and procedure. A pierced PDMS layer was attached to a glass coverslip to shape a 2 × 2 grid of cavities, each 3.5 mm in diameter and 4 mm deep. Neurons were plated on these cavities forming independent, mm-sized neuronal networks, and cultured in identical conditions. For measurements, one of the cavities was left as control, while the others were dosed with specific chemical agents. (B) Left: Bright field image of a typical preparation at day in vitro 8, showing the 4 cavities containing the neuronal networks. Dark circular objects are aggregates of neurons (clusters) connected to one another through bundles of neurites. Right: Fluorescence image of the bottom-right culture. Firing clusters appear as bright spots on the images. (C) Representative fluorescence traces of the 4 clusters highlighted in (B), and along 15 min of recording. The yellow boxes illustrate different combinations of co-activations. Clusters #1 and #2 always fire together and shape a strong, persistent community.

Mentions: We used primary cultures of rat embryonic cortical neurons in our experiments. To study the influence of chemical perturbations on their activity, we developed a simple yet advantageous experimental platform consisting in an array of 2 × 2 cavities pierced on a PDMS layer, each cavity 3.5 mm in diameter and 4 mm deep (see Methods and Fig. 1A). Neurons were seeded with identical nominal density in each cavity, and the entire system cultured as a single unit in a multi-well culture plate to ensure identical development.


Magnetite-Amyloid-β deteriorates activity and functional organization in an in vitro model for Alzheimer's disease.

Teller S, Tahirbegi IB, Mir M, Samitier J, Soriano J - Sci Rep (2015)

Experiments and data acquisition.(A) Sketch of the experimental setup and procedure. A pierced PDMS layer was attached to a glass coverslip to shape a 2 × 2 grid of cavities, each 3.5 mm in diameter and 4 mm deep. Neurons were plated on these cavities forming independent, mm-sized neuronal networks, and cultured in identical conditions. For measurements, one of the cavities was left as control, while the others were dosed with specific chemical agents. (B) Left: Bright field image of a typical preparation at day in vitro 8, showing the 4 cavities containing the neuronal networks. Dark circular objects are aggregates of neurons (clusters) connected to one another through bundles of neurites. Right: Fluorescence image of the bottom-right culture. Firing clusters appear as bright spots on the images. (C) Representative fluorescence traces of the 4 clusters highlighted in (B), and along 15 min of recording. The yellow boxes illustrate different combinations of co-activations. Clusters #1 and #2 always fire together and shape a strong, persistent community.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4660300&req=5

f1: Experiments and data acquisition.(A) Sketch of the experimental setup and procedure. A pierced PDMS layer was attached to a glass coverslip to shape a 2 × 2 grid of cavities, each 3.5 mm in diameter and 4 mm deep. Neurons were plated on these cavities forming independent, mm-sized neuronal networks, and cultured in identical conditions. For measurements, one of the cavities was left as control, while the others were dosed with specific chemical agents. (B) Left: Bright field image of a typical preparation at day in vitro 8, showing the 4 cavities containing the neuronal networks. Dark circular objects are aggregates of neurons (clusters) connected to one another through bundles of neurites. Right: Fluorescence image of the bottom-right culture. Firing clusters appear as bright spots on the images. (C) Representative fluorescence traces of the 4 clusters highlighted in (B), and along 15 min of recording. The yellow boxes illustrate different combinations of co-activations. Clusters #1 and #2 always fire together and shape a strong, persistent community.
Mentions: We used primary cultures of rat embryonic cortical neurons in our experiments. To study the influence of chemical perturbations on their activity, we developed a simple yet advantageous experimental platform consisting in an array of 2 × 2 cavities pierced on a PDMS layer, each cavity 3.5 mm in diameter and 4 mm deep (see Methods and Fig. 1A). Neurons were seeded with identical nominal density in each cavity, and the entire system cultured as a single unit in a multi-well culture plate to ensure identical development.

Bottom Line: Recent studies have shown that other agents, in particular magnetite, can also play a pivotal role.Our work suggests that magnetite nanoparticles have a more prominent role in AD than previously thought, and may bring new insights in the understanding of the damaging action of magnetite-amyloid-β complex.Our experimental system also offers new interesting perspectives to explore key biochemical players in neurological disorders through a controlled, model system manner.

View Article: PubMed Central - PubMed

Affiliation: Departament d'Estructura i Constituents de la Matèria, Universitat de Barcelona, Barcelona, E-08028, Spain.

ABSTRACT
The understanding of the key mechanisms behind human brain deterioration in Alzheimer' disease (AD) is a highly active field of research. The most widespread hypothesis considers a cascade of events initiated by amyloid-β peptide fibrils that ultimately lead to the formation of the lethal amyloid plaques. Recent studies have shown that other agents, in particular magnetite, can also play a pivotal role. To shed light on the action of magnetite and amyloid-β in the deterioration of neuronal circuits, we investigated their capacity to alter spontaneous activity patterns in cultured neuronal networks. Using a versatile experimental platform that allows the parallel monitoring of several cultures, the activity in controls was compared with the one in cultures dosed with magnetite, amyloid-β and magnetite-amyloid-β complex. A prominent degradation in spontaneous activity was observed solely when amyloid-β and magnetite acted together. Our work suggests that magnetite nanoparticles have a more prominent role in AD than previously thought, and may bring new insights in the understanding of the damaging action of magnetite-amyloid-β complex. Our experimental system also offers new interesting perspectives to explore key biochemical players in neurological disorders through a controlled, model system manner.

No MeSH data available.


Related in: MedlinePlus