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Cited by 53Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchNeural dynamics and brain function

Inflammatory cytokine-induced changes in neural network activity measured by waveform analysis of high-content calcium imaging in murine cortical neurons

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Clarkson, Benjamin D. S., Kahoud, Robert J., McCarthy, Christina B., Howe, Charles L.·2017·Scientific Reports
DOI 10.1038/s41598-017-09182-5PMC PMC5567248
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Abstract

During acute neuroinflammation, increased levels of cytokines within the brain may contribute to synaptic reorganization that results in long-term changes in network hyperexcitability. Indeed, inflammatory cytokines are implicated in synaptic dysfunction in epilepsy and in an array of degenerative and autoimmune diseases of the central nervous system. Current tools for studying the impact of inflammatory factors on neural networks are either insufficiently fast and sensitive or require complicated and costly experimental rigs. Calcium imaging offers a reasonable surrogate for direct measurement of neuronal network activity, but traditional imaging paradigms are confounded by cellular heterogeneity and cannot readily distinguish between glial and neuronal calcium transients. While the establishment of pure neuron cultures is possible, the removal of glial cells ignores physiologically relevant cell-cell interactions that may be critical for circuit level disruptions induced by inflammatory factors. To overcome these issues, we provide techniques and algorithms for image processing and waveform feature extraction using automated analysis of spontaneous and evoked calcium transients in primary murine cortical neuron cultures transduced with an adeno-associated viral vector driving the GCaMP6f reporter behind a synapsin promoter. Using this system, we provide evidence of network perturbations induced by the inflammatory cytokines TNFα, IL1β, and IFNγ.

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  • A cascade of events following cytokine alterations may result in hyperexcitability of the neuronal network, which is important in the pathophysiology of Alzheimer's disease.

    “This cascade of events may result in hyperexcitability of the neuronal network, which is important in the pathophysiology of AD (Clarkson et al., 2017; Targa Dias Anastacio, Matosin and Ooi, 2022).”

    From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Clarkson et al., 2017

    The Results and Discussion (page numbers unavailable) support the proposed link between inflammatory cytokines, disrupted GABAergic signaling, and neuronal network hyperexcitability in murine cortical cultures. They do not establish that this mechanism is important in Alzheimer’s disease pathophysiology; Alzheimer’s disease appears in reference titles, not in the paper’s stated findings on hyperexcitability. (LLM, conf=0.88)

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Authors
Clarkson, B. D. S., Kahoud, R. J., McCarthy, C. B., & Howe, C. L.
Affiliations
Mayo Clinic (US)
Corresponding author
Howe, Charles L.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2017-08-22
Volume
7
Issue
1
Pages
9037-9037
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-017-09182-5
PMC
PMC5567248
OpenAlex
W2749335674
Cited by
53
References
94
Citations by year
2026: 4 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 7 · 2021: 15 · 2020: 2 · 2019: 5 · 2018: 2
FWCI
1.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Mayo Clinic
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS064571)
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
inflammatory cytokines, neuroinflammation, neuronal network activity, calcium imaging, GCaMP6f, cortical neurons, TNF-α, IL-1β, interferon-gamma, waveform analysis, spontaneous calcium transients, synaptic remodeling, network hyperexcitability, neuron-glia interactions, synapsin promoter, adeno-associated virus vectors, epilepsy
MeSH terms
Animals, Calcium, Cells, Cultured, Cerebral Cortex, Fluorescent Antibody Technique, Nerve Net, Neural Pathways, Neurons, Biomarkers, Gene Expression, Cytokines, Receptors, Neurotransmitter, Inflammation Mediators, Calcium Signaling, Mice, Molecular Imaging

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