Evidence map›Paper›PMID 39501607›Full record

ArticleJournal of Alzheimer's disease : JAD2024

Primary cortical cell tri-culture to study effects of amyloid-β on microglia function and neuroinflammatory response.

Hyehyun Kim, Bryan Le, Noah Goshi, Kan Zhu, Ana Cristina Grodzki, Pamela J Lein, Min Zhao, Erkin Seker

Abstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Hyehyun KimDepartment of Biomedical Engineering, University of California-Davis, Davis, CA, USA.
Bryan LeDepartment of Ophthalmology and Vision Science, University of California-Davis, Davis, CA, USA.
Noah GoshiDepartment of Biomedical Engineering, University of California-Davis, Davis, CA, USA.
Kan ZhuDepartment of Ophthalmology and Vision Science, University of California-Davis, Davis, CA, USA.
Ana Cristina GrodzkiDepartment of Molecular Biosciences, University of California-Davis, Davis, CA, USA.
Pamela J LeinDepartment of Molecular Biosciences, University of California-Davis, Davis, CA, USA.
Min ZhaoDepartment of Ophthalmology and Vision Science, University of California-Davis, Davis, CA, USA.
Erkin SekerDepartment of Electrical and Computer Engineering, University of California-Davis, Davis, CA, USA.ORCID 0000-0003-2401-3562

Funding

UC Davis Environmental Health Sciences Core CenterP30ES023513 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Irva Hertz-Picciotto · 2015 to 2026
$26.0M
Research Project: Pathologic Significance of Maternal AutoantibodiesP50HD103526 · NICHD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEONARD J. ABBEDUTO, Melissa Dawn Bauman · 2020 to 2026
$9.7M
Vision Science Training Program: Cornea to CortexT32EY015387 · NEI · UNIVERSITY OF CALIFORNIA DAVIS · PI MARIE E BURNS · 2003 to 2026
$4.8M
Bottom-up, high-throughput prototyping of extracellular vesicle mimetics using cell-free synthetic biologyR01EB034279 · NIBIB · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Randy Carney, Cheemeng Tan · 2023 to 2026
$2.5M
Neuronal Contribution to the Propagation of Inflammation in the Central Nervous SystemR03NS118156 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SEKER, ERKIN · 2020 to 2021
$216k
NEI NIH HHS T32 EY015387NIBIB NIH HHS R01 EB034279NICHD NIH HHS P50 HD103526NIEHS NIH HHS P30 ES023513NINDS NIH HHS R03 NS118156
6 · The paper itself

Abstract

backgroundMicroglia play a critical role in neurodegenerative disorders, such as Alzheimer's disease, where alterations in microglial function may result in pathogenic amyloid-β (Aβ) accumulation, chronic neuroinflammation, and deleterious effects on neuronal function. However, studying these complex factors in vivo, where numerous confounding processes exist, is challenging, and until recently, in vitro models have not allowed sustained culture of critical cell types in the same culture.

objectiveWe employed a rat primary tri-culture (neurons, astrocytes, and microglia) model and compared it to co-culture (neurons and astrocytes) and mono-culture (microglia) to study microglial function (i.e., motility and Aβ clearance) and proteomic response to exogenous Aβ.

methodsThe cultures were exposed to fluorescently-labeled Aβ (FITC-Aβ) particles for varying durations. Epifluorescence microscopy images were analyzed to quantify the number of FITC-Aβ particles and assess cytomorphological features. Cytokine profiles from conditioned media were obtained. Live-cell imaging was employed to extract microglia motility parameters.

resultsFITC-Aβ particles were more effectively cleared in the tri-culture compared to the co-culture. This was attributed to microglia engulfing FITC-Aβ particles, as confirmed via epifluorescence and confocal microscopy. FITC-Aβ treatment significantly increased microglia size, but had no significant effect on neuronal surface coverage or astrocyte size. Upon FITC-Aβ treatment, there was a significant increase in proinflammatory cytokines in tri-culture, but not in co-culture. Aβ treatment altered microglia motility evident as a swarming-like motion.

conclusionsThe results suggest that neuron-astrocyte-microglia interactions influence microglia function and highlight the utility of the tri-culture model for studies of neuroinflammation, neurodegeneration, and cell-cell communication.

Indexed as

Amyloid beta-PeptidesAstrocytesCerebral CortexCoculture TechniquesMicrogliaNeuronsAnimalsCells, CulturedCytokinesNeuroinflammatory DiseasesRatsRats, Sprague-DawleyAmyloid beta-PeptidesCytokinesAlzheimer's diseaseamyloid-betacell motilitycytokine profilelive cell imagingmicroglianeural cell cultureneuroinflammationphagocytosis

Identifiers

PMID39501607
PMCPMC11758989

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.