Lipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues

Abstract Three-dimensional (3D) neural microtissues are a powerful in vitro paradigm for studying brain development and disease under controlled conditions, while maintaining many key attributes of the in vivo environment. Here, we used primary cortical microtissues to study the effects of neuroinfl...

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Autores principales:	Elaina Atherton, Sophie Brown, Emily Papiez, Maria I. Restrepo, David A. Borton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3e89879fe89042f38daeecf27522a519
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spelling	oai:doaj.org-article:3e89879fe89042f38daeecf27522a5192021-11-21T12:25:07ZLipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues10.1038/s41598-021-01616-52045-2322https://doaj.org/article/3e89879fe89042f38daeecf27522a5192021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01616-5https://doaj.org/toc/2045-2322Abstract Three-dimensional (3D) neural microtissues are a powerful in vitro paradigm for studying brain development and disease under controlled conditions, while maintaining many key attributes of the in vivo environment. Here, we used primary cortical microtissues to study the effects of neuroinflammation on neural microcircuits. We demonstrated the use of a genetically encoded calcium indicator combined with a novel live-imaging platform to record spontaneous calcium transients in microtissues from day 14–34 in vitro. We implemented graph theory analysis of calcium activity to characterize underlying functional connectivity and community structure of microcircuits, which are capable of capturing subtle changes in network dynamics during early disease states. We found that microtissues cultured for 34 days displayed functional remodeling of microcircuits and that community structure strengthened over time. Lipopolysaccharide, a neuroinflammatory agent, significantly increased functional connectivity and disrupted community structure 5–9 days after exposure. These microcircuit-level changes have broad implications for the role of neuroinflammation in functional dysregulation of neural networks.Elaina AthertonSophie BrownEmily PapiezMaria I. RestrepoDavid A. BortonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elaina Atherton Sophie Brown Emily Papiez Maria I. Restrepo David A. Borton Lipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues
description	Abstract Three-dimensional (3D) neural microtissues are a powerful in vitro paradigm for studying brain development and disease under controlled conditions, while maintaining many key attributes of the in vivo environment. Here, we used primary cortical microtissues to study the effects of neuroinflammation on neural microcircuits. We demonstrated the use of a genetically encoded calcium indicator combined with a novel live-imaging platform to record spontaneous calcium transients in microtissues from day 14–34 in vitro. We implemented graph theory analysis of calcium activity to characterize underlying functional connectivity and community structure of microcircuits, which are capable of capturing subtle changes in network dynamics during early disease states. We found that microtissues cultured for 34 days displayed functional remodeling of microcircuits and that community structure strengthened over time. Lipopolysaccharide, a neuroinflammatory agent, significantly increased functional connectivity and disrupted community structure 5–9 days after exposure. These microcircuit-level changes have broad implications for the role of neuroinflammation in functional dysregulation of neural networks.
format	article
author	Elaina Atherton Sophie Brown Emily Papiez Maria I. Restrepo David A. Borton
author_facet	Elaina Atherton Sophie Brown Emily Papiez Maria I. Restrepo David A. Borton
author_sort	Elaina Atherton
title	Lipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues
title_short	Lipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues
title_full	Lipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues
title_fullStr	Lipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues
title_full_unstemmed	Lipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues
title_sort	lipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3e89879fe89042f38daeecf27522a519
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Lipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues

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