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Progressive striatonigral degeneration in a transgenic mouse model of multiple system atrophy: translational implications for interventional therapies

Overview of attention for article published in Acta Neuropathologica Communications, January 2018
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  • Above-average Attention Score compared to outputs of the same age (63rd percentile)
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5 tweeters
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2 Facebook pages

Citations

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36 Dimensions

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52 Mendeley
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Title
Progressive striatonigral degeneration in a transgenic mouse model of multiple system atrophy: translational implications for interventional therapies
Published in
Acta Neuropathologica Communications, January 2018
DOI 10.1186/s40478-017-0504-y
Pubmed ID
Authors

Violetta Refolo, Francesco Bez, Alexia Polissidis, Daniela Kuzdas-Wood, Edith Sturm, Martina Kamaratou, Werner Poewe, Leonidas Stefanis, M. Angela Cenci, Marina Romero-Ramos, Gregor K. Wenning, Nadia Stefanova

Abstract

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by widespread oligodendroglial cytoplasmic inclusions of filamentous α-synuclein, and neuronal loss in autonomic centres, basal ganglia and cerebellar circuits. It has been suggested that primary oligodendroglial α-synucleinopathy may represent a trigger in the pathogenesis of MSA, but the mechanisms underlying selective vulnerability and disease progression are unclear. The post-mortem analysis of MSA brains provides a static final picture of the disease neuropathology, but gives no clear indication on the sequence of pathogenic events in MSA. Therefore, alternative methods are needed to address these issues. We investigated selective vulnerability and disease progression in the transgenic PLP-α-syn mouse model of MSA characterized by targeted oligodendroglial α-synuclein overexpression aiming to provide a neuropathological correlate of motor deterioration. We show progressive motor deficits that emerge at 6 months of age and deteriorate up to 18 months of follow-up. The motor phenotype was associated with dopaminergic cell loss in the substantia nigra pars compacta at 6 months, followed by loss of striatal dopaminergic terminals and DARPP32-positive medium sized projection neurons at 12 months. Olivopontocerebellar motor loops remained spared in the PLP-α-syn model of MSA. These findings replicate progressive striatonigral degeneration underlying Parkinson-variant MSA. The initiation of the degenerative process was linked to an increase of soluble oligomeric α-synuclein species between 2 and 6 months. Early region-specific α-synuclein-associated activation profile of microglia was found in MSA substantia nigra. The role of abnormal neuroinflammatory signalling in disease progression was further supported by increased levels of CD68, CCL3, CCL5 and M-CSF with a peak in aged PLP-α-syn mice. In summary, transgenic PLP-α-syn mice show a distinctive oligodendroglial α-synucleinopathy that is associated with progressive striatonigral degeneration linked to abnormal neuroinflammatory response. The model provides a relevant tool for preclinical therapeutic target discovery for human Parkinson-variant MSA.

Twitter Demographics

The data shown below were collected from the profiles of 5 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 52 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 17%
Researcher 7 13%
Student > Master 6 12%
Student > Bachelor 4 8%
Student > Doctoral Student 3 6%
Other 10 19%
Unknown 13 25%
Readers by discipline Count As %
Neuroscience 10 19%
Medicine and Dentistry 9 17%
Biochemistry, Genetics and Molecular Biology 3 6%
Veterinary Science and Veterinary Medicine 2 4%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Other 11 21%
Unknown 15 29%

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 August 2018.
All research outputs
#4,151,725
of 13,804,624 outputs
Outputs from Acta Neuropathologica Communications
#395
of 726 outputs
Outputs of similar age
#138,792
of 394,828 outputs
Outputs of similar age from Acta Neuropathologica Communications
#48
of 90 outputs
Altmetric has tracked 13,804,624 research outputs across all sources so far. This one is in the 49th percentile – i.e., 49% of other outputs scored the same or lower than it.
So far Altmetric has tracked 726 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.1. This one is in the 44th percentile – i.e., 44% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 394,828 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.
We're also able to compare this research output to 90 others from the same source and published within six weeks on either side of this one. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.