Evidence map›Paper›PMID 29955902›Full record

ArticleArchives of toxicology2018

Toxicity, recovery, and resilience in a 3D dopaminergic neuronal in vitro model exposed to rotenone.

Georgina Harris, Melanie Eschment, Sebastian Perez Orozco, J Michael McCaffery, Richard Maclennan, Daniel Severin, Marcel Leist, Andre Kleensang, David Pamies, Alexandra Maertens and 5 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Archives of toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
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

27 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
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  5. Establishment of a Depression Model Using Dexamethasone-treated Three-dimensional Cultured Rat Cortical Cells.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 2 countries.

Georgina HarrisCenter for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Melanie EschmentCenter for Alternatives to Animal Testing (CAAT) Europe, Department of Biology, University of Konstanz, Konstanz, Germany.
Sebastian Perez OrozcoThe Integrated Imaging Center, Department of Biology, Engineering in Oncology Center and The Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
J Michael McCafferyThe Integrated Imaging Center, Department of Biology, Engineering in Oncology Center and The Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
Richard MaclennanCyprotex Discovery Ltd., Macclesfield, UK.
Daniel SeverinThe Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USA.
Marcel LeistCenter for Alternatives to Animal Testing (CAAT) Europe, Department of Biology, University of Konstanz, Konstanz, Germany.
Andre KleensangCenter for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
David PamiesCenter for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Alexandra MaertensCenter for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Helena T HogbergCenter for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Dana FreemanDepartment of Environmental Health and Engineering, Johns Hopkins University, Baltimore, MD, USA.
Alfredo KirkwoodThe Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USA.
Thomas HartungCenter for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Lena SmirnovaCenter for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. lsmirno1@jhu.edu.ORCID http://orcid.org/0000-0003-0171-3881
Johns Hopkins University · USAllen Institute for Brain Science · USUniversity of Konstanz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To date, most in vitro toxicity testing has focused on acute effects of compounds at high concentrations. This testing strategy does not reflect real-life exposures, which might contribute to long-term disease outcome. We used a 3D-human dopaminergic in vitro LUHMES cell line model to determine whether effects of short-term rotenone exposure (100 nM, 24 h) are permanent or reversible. A decrease in complex I activity, ATP, mitochondrial diameter, and neurite outgrowth were observed acutely. After compound removal, complex I activity was still inhibited; however, ATP levels were increased, cells were electrically active and aggregates restored neurite outgrowth integrity and mitochondrial morphology. We identified significant transcriptomic changes after 24 h which were not present 7 days after wash-out. Our results suggest that testing short-term exposures in vitro may capture many acute effects which cells can overcome, missing adaptive processes, and long-term mechanisms. In addition, to study cellular resilience, cells were re-exposed to rotenone after wash-out and recovery period. Pre-exposed cells maintained higher metabolic activity than controls and presented a different expression pattern in genes previously shown to be altered by rotenone. NEF2L2, ATF4, and EAAC1 were downregulated upon single hit on day 14, but unchanged in pre-exposed aggregates. DAT and CASP3 were only altered after re-exposure to rotenone, while TYMS and MLF1IP were downregulated in both single-exposed and pre-exposed aggregates. In summary, our study shows that a human cell-based 3D model can be used to assess cellular adaptation, resilience, and long-term mechanisms relevant to neurodegenerative research.

Indexed as

Adenosine TriphosphateCell Culture TechniquesDopaminergic NeuronsGene Expression RegulationHumansInsecticidesMitochondriaNeuronal OutgrowthRotenoneToxicity TestsAdenosine TriphosphateInsecticidesRotenone3D LUHMESCellular defenceGene responseNeurodegenerationPesticideRecoveryResilienceRotenone

Identifiers

PMID29955902
PMCPMC6063347
OpenAlexW2810554584

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.