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Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates

Overview of attention for article published in Acta Neuropathologica Communications, June 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (89th percentile)
  • Good Attention Score compared to outputs of the same age and source (78th percentile)

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2 news outlets
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1 X user
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3 patents

Citations

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33 Dimensions

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62 Mendeley
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Title
Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates
Published in
Acta Neuropathologica Communications, June 2017
DOI 10.1186/s40478-017-0451-7
Pubmed ID
Authors

Ronald J. Mandel, David J. Marmion, Deniz Kirik, Yaping Chu, Clifford Heindel, Thomas McCown, Steven J. Gray, Jeffrey H. Kordower

Abstract

Multiple system atrophy (MSA) is a horrible and unrelenting neurodegenerative disorder with an uncertain etiology and pathophysiology. MSA is a unique proteinopathy in which alpha-synuclein (α-syn) accumulates preferentially in oligodendroglia rather than neurons. Glial cytoplasmic inclusions (GCIs) of α-syn are thought to elicit changes in oligodendrocyte function, such as reduced neurotrophic support and demyelination, leading to neurodegeneration. To date, only a murine model using one of three promoters exist to study this disease. We sought to develop novel rat and nonhuman primate (NHP) models of MSA by overexpressing α-syn in oligodendroglia using a novel oligotrophic adeno-associated virus (AAV) vector, Olig001. To establish tropism, rats received intrastriatal injections of Olig001 expressing GFP. Histological analysis showed widespread expression of GFP throughout the striatum and corpus callosum with >95% of GFP+ cells co-localizing with oligodendroglia and little to no expression in neurons or astrocytes. We next tested the efficacy of this vector in rhesus macaques with intrastriatal injections of Olig001 expressing GFP. As in rats, we observed a large number of GFP+ cells in gray matter and white matter tracts of the striatum and the corpus callosum, with 90-94% of GFP+ cells co-localizing with an oligodendroglial marker. To evaluate the potential of our vector to elicit MSA-like pathology in NHPs, we injected rhesus macaques intrastriatally with Olig001 expressing the α-syn transgene. Histological analysis 3-months after injection demonstrated widespread α-syn expression throughout the striatum as determined by LB509 and phosphorylated serine-129 α-syn immunoreactivity, all of which displayed as tropism similar to that seen with GFP. As in MSA, Olig001-α-syn GCIs in our model were resistant to proteinase K digestion and caused microglial activation. Critically, demyelination was observed in the white matter tracts of the corpus callosum and striatum of Olig001-α-syn but not Olig001-GFP injected animals, similar to the human disease. These data support the concept that this vector can provide novel rodent and nonhuman primate models of MSA.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 62 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 16%
Student > Master 9 15%
Student > Bachelor 9 15%
Researcher 7 11%
Other 4 6%
Other 10 16%
Unknown 13 21%
Readers by discipline Count As %
Neuroscience 14 23%
Biochemistry, Genetics and Molecular Biology 11 18%
Medicine and Dentistry 3 5%
Business, Management and Accounting 2 3%
Agricultural and Biological Sciences 2 3%
Other 12 19%
Unknown 18 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 20. 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 19 September 2023.
All research outputs
#1,565,815
of 22,981,247 outputs
Outputs from Acta Neuropathologica Communications
#150
of 1,391 outputs
Outputs of similar age
#30,699
of 291,513 outputs
Outputs of similar age from Acta Neuropathologica Communications
#5
of 23 outputs
Altmetric has tracked 22,981,247 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,391 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.8. This one has done well, scoring higher than 89% of its peers.
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 291,513 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.