High-resolution bioelectrical imaging of Aß-induced network dysfunction on CMOS-MEAs for neurotoxicity and rescue studies.
Sci Rep
; 7(1): 2460, 2017 05 26.
Article
em En
| MEDLINE
| ID: mdl-28550283
ABSTRACT
Neurotoxicity and the accumulation of extracellular amyloid-beta1-42 (Aß) 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 Aß-neurotoxicity. We also demonstrate the potential of this in vitro model to test a plausible hypothesis underlying the Aß-neurotoxicity and to assay potential therapeutic approaches. Specifically, by quantifying N-methyl D-aspartate (NMDA) concentration-dependent effects in comparison with low-concentration allogenic-Aß, we confirm the role of extrasynaptic-NMDA receptors activation that may contribute to Aß-neurotoxicity. Finally, we assess the potential rescue of neural stem cells (NSCs) and of two pharmacotherapies, memantine and saffron, for reversing Aß-neurotoxicity and rescuing network-wide firing.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Memantina
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Peptídeos beta-Amiloides
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Receptores de N-Metil-D-Aspartato
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Hipocampo
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Neurônios
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Antiparkinsonianos
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Itália