Evidence map›Paper›PMID 39962601›Full record

ArticleActa neuropathologica communications2025

Bradykinesia and postural instability in a model of prodromal synucleinopathy with α-synuclein aggregation initiated in the gigantocellular nuclei.

Vasileios Theologidis, Sara A Ferreira, Nanna M Jensen, Diana Gomes Moreira, Ole A Ahlgreen, Mads W Hansen, Emilie D Rosenberg, Mette Richner, Islam Faress, Hjalte Gram and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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

18 authors.

Vasileios TheologidisDepartment of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 35, 8200, Aarhus, Denmark.
Sara A FerreiraDepartment of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000, Aarhus, Denmark.
Nanna M JensenDepartment of Biomedicine, Danish Research Institute of Translational Neuroscience (DANDRITE), Aarhus University, Ole Worms Allé 3, 8000, Aarhus C, Denmark.
Diana Gomes MoreiraDepartment of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 35, 8200, Aarhus, Denmark.
Ole A AhlgreenDepartment of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000, Aarhus, Denmark.
Mads W HansenDepartment of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000, Aarhus, Denmark.
Emilie D RosenbergDepartment of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000, Aarhus, Denmark.
Mette RichnerDepartment of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000, Aarhus, Denmark.
Islam FaressDepartment of Biomedicine, Danish Research Institute of Translational Neuroscience (DANDRITE), Aarhus University, Ole Worms Allé 3, 8000, Aarhus C, Denmark.
Hjalte GramDepartment of Biomedicine, Danish Research Institute of Translational Neuroscience (DANDRITE), Aarhus University, Ole Worms Allé 3, 8000, Aarhus C, Denmark.
Poul Henning JensenDepartment of Biomedicine, Danish Research Institute of Translational Neuroscience (DANDRITE), Aarhus University, Ole Worms Allé 3, 8000, Aarhus C, Denmark.
Per BorghammerDepartment of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 35, 8200, Aarhus, Denmark.
Jens R NyengaardDepartment of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 35, 8200, Aarhus, Denmark.
Marina Romero-RamosDepartment of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000, Aarhus, Denmark.
Christian B VægterDepartment of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000, Aarhus, Denmark.
Wilma D J van de BergDepartment of Anatomy and Neurosciences, Amsterdam Neuroscience, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Nathalie Van Den BergeDepartment of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 35, 8200, Aarhus, Denmark.
Asad JanDepartment of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, 8000, Aarhus, Denmark. ajan@aias.au.dk.ORCID 0000-0002-3636-0070

Funding

Lundbeck Foundation R383-2022-180Michael J. Fox Foundation for Parkinson's Research MJFF-021498
6 · The paper itself

Abstract

α-Synuclein (aSyn) accumulation within the extra-nigral neuronal populations in the brainstem, including the gigantocellular nuclei (GRN/Gi) of reticular formation, is a recognized feature during the prodromal phase of Parkinson disease (PD). Accordingly, there is a burgeoning interest in animal model development for understanding the pathological significance of extra-nigral synucleinopathy, in relation to motor and/or non-motor symptomatology in PD. Here, we report an experimental paradigm for the induction of aSyn aggregation in brainstem, with stereotaxic delivery of pre-formed fibrillar (PFF) aSyn in the pontine GRN of transgenic mice expressing the mutant human Ala53Thr aSyn (M83 line). Our data show that PFF aSyn-induced aggregate pathology in GRN and distinct nuclei of subcortical motor system leads to progressive decline in home cage activity, which was accompanied by postural instability and impaired motor coordination. The progressive accumulation of aSyn pathology in brainstem and motor neurons in lumbar spinal cord heralded the onset of a moribund stage, which culminated in impaired survival. Collectively, our observations suggest an experimental framework for studying the pathological significance of aSyn aggregation in GRN in relation to features of movement disability in PD. With further refinements, we anticipate that this model holds promise as a test-bed for translational research in PD and related disorders.

Indexed as

alpha-SynucleinBrain StemHypokinesiaPostural BalanceProtein Aggregation, PathologicalSynucleinopathiesAnimalsDisease Models, AnimalHumansMaleMiceMice, TransgenicParkinson DiseaseProdromal Symptomsalpha-SynucleinGigantocellular nucleusLewy pathologyParkinson diseaseΑlpha-synuclein

Identifiers

PMID39962601
PMCPMC11834571

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LicenceCC BY-NC-ND
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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.