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High-resolution bioelectrical imaging of Aβ-induced network dysfunction on CMOS-MEAs for neurotoxicity and rescue studies

Neurotoxicity and the accumulation of extracellular amyloid-beta(1–42) (Aβ) peptides are associated with the development of Alzheimer’s disease (AD) and correlate with neuronal activity and network dysfunctions, ultimately leading to cellular death. However, research on neurodegenerative diseases is...

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Autores principales: Amin, Hayder, Nieus, Thierry, Lonardoni, Davide, Maccione, Alessandro, Berdondini, Luca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446416/
https://www.ncbi.nlm.nih.gov/pubmed/28550283
http://dx.doi.org/10.1038/s41598-017-02635-x
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author Amin, Hayder
Nieus, Thierry
Lonardoni, Davide
Maccione, Alessandro
Berdondini, Luca
author_facet Amin, Hayder
Nieus, Thierry
Lonardoni, Davide
Maccione, Alessandro
Berdondini, Luca
author_sort Amin, Hayder
collection PubMed
description Neurotoxicity and the accumulation of extracellular amyloid-beta(1–42) (Aβ) peptides are associated with the development of Alzheimer’s disease (AD) and correlate with neuronal activity and network dysfunctions, ultimately leading to cellular death. However, research on neurodegenerative diseases is hampered by the paucity of reliable readouts and experimental models to study such functional decline from an early onset and to test rescue strategies within networks at cellular resolution. To overcome this important obstacle, we demonstrate a simple yet powerful in vitro AD model based on a rat hippocampal cell culture system that exploits large-scale neuronal recordings from 4096-electrodes on CMOS-chips for electrophysiological quantifications. This model allows us to monitor network activity changes at the cellular level and to uniquely uncover the early activity-dependent deterioration induced by Aβ-neurotoxicity. We also demonstrate the potential of this in vitro model to test a plausible hypothesis underlying the Aβ-neurotoxicity and to assay potential therapeutic approaches. Specifically, by quantifying N-methyl D-aspartate (NMDA) concentration-dependent effects in comparison with low-concentration allogenic-Aβ, we confirm the role of extrasynaptic-NMDA receptors activation that may contribute to Aβ-neurotoxicity. Finally, we assess the potential rescue of neural stem cells (NSCs) and of two pharmacotherapies, memantine and saffron, for reversing Aβ-neurotoxicity and rescuing network-wide firing.
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spelling pubmed-54464162017-05-30 High-resolution bioelectrical imaging of Aβ-induced network dysfunction on CMOS-MEAs for neurotoxicity and rescue studies Amin, Hayder Nieus, Thierry Lonardoni, Davide Maccione, Alessandro Berdondini, Luca Sci Rep Article Neurotoxicity and the accumulation of extracellular amyloid-beta(1–42) (Aβ) peptides are associated with the development of Alzheimer’s disease (AD) and correlate with neuronal activity and network dysfunctions, ultimately leading to cellular death. However, research on neurodegenerative diseases is hampered by the paucity of reliable readouts and experimental models to study such functional decline from an early onset and to test rescue strategies within networks at cellular resolution. To overcome this important obstacle, we demonstrate a simple yet powerful in vitro AD model based on a rat hippocampal cell culture system that exploits large-scale neuronal recordings from 4096-electrodes on CMOS-chips for electrophysiological quantifications. This model allows us to monitor network activity changes at the cellular level and to uniquely uncover the early activity-dependent deterioration induced by Aβ-neurotoxicity. We also demonstrate the potential of this in vitro model to test a plausible hypothesis underlying the Aβ-neurotoxicity and to assay potential therapeutic approaches. Specifically, by quantifying N-methyl D-aspartate (NMDA) concentration-dependent effects in comparison with low-concentration allogenic-Aβ, we confirm the role of extrasynaptic-NMDA receptors activation that may contribute to Aβ-neurotoxicity. Finally, we assess the potential rescue of neural stem cells (NSCs) and of two pharmacotherapies, memantine and saffron, for reversing Aβ-neurotoxicity and rescuing network-wide firing. Nature Publishing Group UK 2017-05-26 /pmc/articles/PMC5446416/ /pubmed/28550283 http://dx.doi.org/10.1038/s41598-017-02635-x Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Amin, Hayder
Nieus, Thierry
Lonardoni, Davide
Maccione, Alessandro
Berdondini, Luca
High-resolution bioelectrical imaging of Aβ-induced network dysfunction on CMOS-MEAs for neurotoxicity and rescue studies
title High-resolution bioelectrical imaging of Aβ-induced network dysfunction on CMOS-MEAs for neurotoxicity and rescue studies
title_full High-resolution bioelectrical imaging of Aβ-induced network dysfunction on CMOS-MEAs for neurotoxicity and rescue studies
title_fullStr High-resolution bioelectrical imaging of Aβ-induced network dysfunction on CMOS-MEAs for neurotoxicity and rescue studies
title_full_unstemmed High-resolution bioelectrical imaging of Aβ-induced network dysfunction on CMOS-MEAs for neurotoxicity and rescue studies
title_short High-resolution bioelectrical imaging of Aβ-induced network dysfunction on CMOS-MEAs for neurotoxicity and rescue studies
title_sort high-resolution bioelectrical imaging of aβ-induced network dysfunction on cmos-meas for neurotoxicity and rescue studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446416/
https://www.ncbi.nlm.nih.gov/pubmed/28550283
http://dx.doi.org/10.1038/s41598-017-02635-x
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