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Cited by 10Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchNeural dynamics and brain function

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

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Atherton, Elaina, Brown, Sophie, Papiez, Emily, Restrepo, Maria I., Borton, David A.·2021·Scientific Reports
DOI 10.1038/s41598-021-01616-5PMC PMC8595892

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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.

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  • The study accounted for established pathways of astrocyte-microglia cross-talk by using direct cytokine stimulation in 2D cultures lacking microglia and LPS-induced microglial activation in organoids.

    “Our approach accounted for established pathways of astrocyte-microglia cross-talk (8, 9, 15, 40), using direct cytokine stimulation (TNF-α and IL-1β) in 2D cultures lacking microglia and LPS-induced microglial activation in organoids (41)”

    From Varicose projection astrocytes: Conserved reactive cells in brain pathology (2026) · cites this paper as [41]

    The Methods (Lipopolysaccharide challenge; page unavailable) report exposing 3D cortical microtissues to LPS, and the Discussion describes LPS-induced changes in glia, including microglia. The paper does not demonstrate microglial activation specifically; its reported outcome is neuronal network activity. It calls the cultures primary cortical microtissues, not organoids. Citation 41 is attached to the LPS portion of the citing sentence, not its separate description of cytokine stimulation in 2D cultures. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Atherton, E., Brown, S., Papiez, E., Restrepo, M. I., & Borton, D. A.
Affiliations
Brown University (US)
Corresponding author
Borton, David A.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2021-11-16
Volume
11
Issue
1
Pages
22303-22303
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-021-01616-5
PMC
PMC8595892
OpenAlex
W3212643714
Cited by
10
References
5
Citations by year
2026: 4 · 2025: 2 · 2023: 2 · 2022: 1 · 2021: 1
FWCI
0.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Brown University (Internal)
  • U.S. Department of Veterans Affairs (N2864-C)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
neuroinflammation, lipopolysaccharide, functional connectivity, community structure, neural microcircuits, calcium imaging, graph theory, spontaneous calcium transients, network dynamics
MeSH terms
Neuroinflammatory Diseases, Animals, Brain, Female, Lipopolysaccharides, Neural Pathways, Rats, Sprague-Dawley, Rats

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