Evidence map›Paper›PMID 35626675›Full record

ArticleCells2022

Modelling α-Synuclein Aggregation and Neurodegeneration with Fibril Seeds in Primary Cultures of Mouse Dopaminergic Neurons.

Aurore Tourville, David Akbar, Olga Corti, Jochen H M Prehn, Ronald Melki, Stéphane Hunot, Patrick P Michel

Open access · goldAbstract read
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

9 citing papers in PubMed, 15 citations in OpenAlex.

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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

7 authors at 2 institutions in 2 countries.

Aurore TourvilleParis Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France.
David AkbarParis Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France.
Olga CortiParis Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France.
Jochen H M PrehnDepartment of Physiology & Medical Physics and FutureNeuro Centre, Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland.
Ronald MelkiMIRCen, CEA and Laboratory of Neurodegenerative Diseases, CNRS, Institut François Jacob, 92265 Fontenay-aux-Roses, France.ORCID 0000-0003-0000-7096
Stéphane HunotParis Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France.
Patrick P MichelParis Brain Institute-ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Sorbonne Université, 75013 Paris, France.ORCID 0000-0001-5607-3119
Centre National de la Recherche Scientifique · FRRoyal College of Surgeons in Ireland · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To model α-Synuclein (αS) aggregation and neurodegeneration in Parkinson's disease (PD), we established cultures of mouse midbrain dopamine (DA) neurons and chronically exposed them to fibrils 91 (F91) generated from recombinant human αS. We found that F91 have an exquisite propensity to seed the aggregation of endogenous αS in DA neurons when compared to other neurons in midbrain cultures. Until two weeks post-exposure, somal aggregation in DA neurons increased with F91 concentrations (0.01-0.75 μM) and the time elapsed since the initiation of seeding, with, however, no evidence of DA cell loss within this time interval. Neither toxin-induced mitochondrial deficits nor genetically induced loss of mitochondrial quality control mechanisms promoted F91-mediated αS aggregation or neurodegeneration under these conditions. Yet, a significant loss of DA neurons (~30%) was detectable three weeks after exposure to F91 (0.5 μM), i.e., at a time point where somal aggregation reached a plateau. This loss was preceded by early deficits in DA uptake. Unlike αS aggregation, the loss of DA neurons was prevented by treatment with GDNF, suggesting that αS aggregation in DA neurons may induce a form of cell death mimicking a state of trophic factor deprivation. Overall, our model system may be useful for exploring PD-related pathomechanisms and for testing molecules of therapeutic interest for this disorder.

Indexed as

alpha-SynucleinParkinson DiseaseAnimalsDopamineDopaminergic NeuronsMesencephalonMicealpha-SynucleinDopaminecell culture modeldopamine neuronsfibril seedsneurodegenerationParkinson diseaseprotein aggregationα-Synuclein

Identifiers

PMID35626675
PMCPMC9139621
OpenAlexW4280576657

What Socratic holds

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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 Socratic graph.