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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

Homogeneous cultures.(A) Raster plots of spontaneous activity before (left) and after (right) application of M-Aβ complex. Spontaneous activity fell by 65% on average. (B) Ratio of the normalized firing rate for homogeneous (averaged over 5 experiments with the respective standard error of the mean) and clustered cultures (15 experiments), and comparing the behavior of the two kind of cultures for the M, Aβ and M-Aβ perturbations. Both culture types behaved similarly except for the M-Aβ condition, where the homogeneous cultures exhibited a significantly higher decay in activity. (*p < 0.05, Kolmogorov-Smirnov test.)
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f8: Homogeneous cultures.(A) Raster plots of spontaneous activity before (left) and after (right) application of M-Aβ complex. Spontaneous activity fell by 65% on average. (B) Ratio of the normalized firing rate for homogeneous (averaged over 5 experiments with the respective standard error of the mean) and clustered cultures (15 experiments), and comparing the behavior of the two kind of cultures for the M, Aβ and M-Aβ perturbations. Both culture types behaved similarly except for the M-Aβ condition, where the homogeneous cultures exhibited a significantly higher decay in activity. (*p < 0.05, Kolmogorov-Smirnov test.)

Mentions: Spontaneous activity in homogeneous cultures is characterized by episodes of collective dynamics (termed network bursts) combined with silent intervals. Figure 8A shows a typical raster plot of activity before and after application of M-Aβ. Network coherence was preserved upon perturbation, but the frequency and regularity of bursting episodes were substantially reduced. The number of bursting episodes kept decreasing as the damage progressed until activity ceased. This behavior contrasted with the one observed in clustered networks, where whole network activity switched to a modular yet highly rich one that lasted for long time. In general we observed that homogeneous cultures became silent much earlier than clustered ones, a result that provides a qualitative evidence for a higher resistance of the latter to damage.


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)

Homogeneous cultures.(A) Raster plots of spontaneous activity before (left) and after (right) application of M-Aβ complex. Spontaneous activity fell by 65% on average. (B) Ratio of the normalized firing rate for homogeneous (averaged over 5 experiments with the respective standard error of the mean) and clustered cultures (15 experiments), and comparing the behavior of the two kind of cultures for the M, Aβ and M-Aβ perturbations. Both culture types behaved similarly except for the M-Aβ condition, where the homogeneous cultures exhibited a significantly higher decay in activity. (*p < 0.05, Kolmogorov-Smirnov test.)
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f8: Homogeneous cultures.(A) Raster plots of spontaneous activity before (left) and after (right) application of M-Aβ complex. Spontaneous activity fell by 65% on average. (B) Ratio of the normalized firing rate for homogeneous (averaged over 5 experiments with the respective standard error of the mean) and clustered cultures (15 experiments), and comparing the behavior of the two kind of cultures for the M, Aβ and M-Aβ perturbations. Both culture types behaved similarly except for the M-Aβ condition, where the homogeneous cultures exhibited a significantly higher decay in activity. (*p < 0.05, Kolmogorov-Smirnov test.)
Mentions: Spontaneous activity in homogeneous cultures is characterized by episodes of collective dynamics (termed network bursts) combined with silent intervals. Figure 8A shows a typical raster plot of activity before and after application of M-Aβ. Network coherence was preserved upon perturbation, but the frequency and regularity of bursting episodes were substantially reduced. The number of bursting episodes kept decreasing as the damage progressed until activity ceased. This behavior contrasted with the one observed in clustered networks, where whole network activity switched to a modular yet highly rich one that lasted for long time. In general we observed that homogeneous cultures became silent much earlier than clustered ones, a result that provides a qualitative evidence for a higher resistance of the latter to damage.

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