Evidence map›Paper›PMID 37567894›Full record

ArticleNPJ Parkinson's disease2023

Transient exposure to rotenone causes degeneration and progressive parkinsonian motor deficits, neuroinflammation, and synucleinopathy.

Amber D Van Laar, Katherine R Webb, Matthew T Keeney, Victor S Van Laar, Alevtina Zharikov, Edward A Burton, Teresa G Hastings, Kelly E Glajch, Warren D Hirst, J Timothy Greenamyre and 1 more

Open access · goldAbstract read
In one paragraph

Article in NPJ Parkinson's disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
13.6field-weighted citation impact, top 1% 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

47 citing papers in PubMed, 66 citations in OpenAlex.

  1. Review
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  4. Alpha-synuclein fibrils induce budding of mitochondrial-derived vesicles.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  5. Gender-specific gene profiling inIBRO neuroscience reports · 2026
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  6. Neurobiology of exercise in Parkinson's disease.Journal of Parkinson's disease · 2026
    Review
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  17. Article
  18. Dynamic redox monitoring in differentiated human neuroblastoma models of Parkinson's disease.Redox report : communications in free radical research · 2025
    Article
  19. Article
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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

11 authors at 2 institutions in 1 country.

Amber D Van LaarPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
Katherine R WebbPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
Matthew T KeeneyPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-4968-3722
Victor S Van LaarPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
Alevtina ZharikovPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
Edward A BurtonPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-8072-4636
Teresa G HastingsPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA.
Kelly E GlajchNeurodegenerative Diseases Research Unit, Biogen, Cambridge, MA, 02142, USA.
Warren D HirstNeurodegenerative Diseases Research Unit, Biogen, Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-0389-8891
J Timothy GreenamyrePittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA. jgreena@pitt.edu.
Emily M RochaPittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA. rocha@pitt.edu.ORCID http://orcid.org/0000-0003-2171-5104
University of Pittsburgh · USBiogen (United States) · US

Funding

VARIABILITY, STABILITY & SMOOTHNESS OF WALKINGP30AG024827 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Caterina Rosano · 2004 to 2026
$28.6M
Pathogenic mechanisms of gene-environment interactions in Parkinson's diseaseR01ES022644 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BURTON, EDWARD ALAN · 2014 to 2018
$1.7M
A slowly progressive, endogenous synucleinopathy model of Parkinson's diseaseR21ES027470 · NIEHS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GREENAMYRE, J TIMOTHY · 2017 to 2018
$427k
Alpha-synuclein RNAi in a model of sporadic Parkinson's diseaseI01BX000548 · VA · VETERANS HEALTH ADMINISTRATION · PI BURTON, EDWARD ALAN · 2009 to 2012
–
BLRD VA I01 BX000548NIA NIH HHS P30 AG024827NIEHS NIH HHS R01 ES022644NIEHS NIH HHS R21 ES027470
6 · The paper itself

Abstract

Individuals with Parkinson's disease (PD) typically receive a diagnosis once they have developed motor symptoms, at which point there is already significant loss of substantia nigra dopamine neurons, α-synuclein accumulation in surviving neurons, and neuroinflammation. Consequently, the point of clinical presentation may be too late to initiate disease-modifying therapy. In contrast to this clinical reality, animal models often involve acute neurodegeneration and potential therapies are tested concurrently or shortly after the pathogenic insult has begun rather than later when diagnostic clinical symptoms emerge. Therefore, we sought to develop a model that reflects the clinical situation more accurately. Middle-aged rats (7-9 months-old) received a single daily intraperitoneal injection of rotenone for 5 consecutive days and were observed over the next 8-9 months. Rotenone-treated rats showed transient motor slowing and postural instability during exposure but recovered within 9 days of rotenone cessation. Rats remained without behavioral deficits for 3-4 months, then developed progressive motor abnormalities over the ensuing months. As motor abnormalities began to emerge 3 months after rotenone exposure, there was significant loss of nigral dopaminergic neurons and significant microglial activation. There was delayed accumulation of α-synuclein in neurons of the substantia nigra and frontal cortex, which was maximal at 9 months post-rotenone. In summary, a brief temporally-remote exposure to rotenone causes delayed and progressive behavioral and neuropathological changes similar to Parkinson's disease. This model mimics the human clinical situation, in which pathogenesis is well-established by the time diagnostic motor deficits appear. As such, this model may provide a more relevant experimental system in which to test disease-modifying therapeutics.

Identifiers

PMID37567894
PMCPMC10421849
OpenAlexW4385763670

What OpenQuestion holds

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Registered trials

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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.