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Colony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice

Overview of attention for article published in Journal of Neuroinflammation, August 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (87th percentile)
  • High Attention Score compared to outputs of the same age and source (85th percentile)

Mentioned by

news
1 news outlet
patent
4 patents

Citations

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374 Dimensions

Readers on

mendeley
408 Mendeley
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Title
Colony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice
Published in
Journal of Neuroinflammation, August 2015
DOI 10.1186/s12974-015-0366-9
Pubmed ID
Authors

Nabil N. Dagher, Allison R. Najafi, Kara M. Neely Kayala, Monica R. P. Elmore, Terra E. White, Rodrigo Medeiros, Brian L. West, Kim N. Green

Abstract

Microglia are dependent upon colony-stimulating factor 1 receptor (CSF1R) signaling for their survival in the adult brain, with administration of the dual CSF1R/c-kit inhibitor PLX3397 leading to the near-complete elimination of all microglia brainwide. Here, we determined the dose-dependent effects of a specific CSF1R inhibitor (PLX5622) on microglia in both wild-type and the 3xTg-AD mouse model of Alzheimer's disease. Wild-type mice were treated with PLX5622 for up to 21 days, and the effects on microglial numbers were assessed. 3xTg-AD mice were treated with PLX5622 for 6 or 12 weeks and effects on microglial numbers and pathology subsequently assessed. High doses of CSF1R inhibitor eliminate most microglia from the brain, but a 75 % lower-dose results in sustained elimination of ~30 % of microglia in both wild-type and 3xTg-AD mice. No behavioral or cognitive deficits were found in mice either depleted of microglia or treated with lower CSF1R inhibitor concentrations. Aged 3xTg-AD mice treated for 6 or 12 weeks with lower levels of PLX5622 resulted in improved learning and memory. Aβ levels and plaque loads were not altered, but microglia in treated mice no longer associated with plaques, revealing a role for the CSF1R in the microglial reaction to plaques, as well as in mediating cognitive deficits. We find that inhibition of CSF1R alone is sufficient to eliminate microglia and that sustained microglial elimination is concentration-dependent. Inhibition of the CSF1R at lower levels in 3xTg-AD mice prevents microglial association with plaques and improves cognition.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 408 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 2 <1%
United States 2 <1%
Unknown 404 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 85 21%
Researcher 60 15%
Student > Bachelor 53 13%
Student > Master 34 8%
Student > Doctoral Student 24 6%
Other 69 17%
Unknown 83 20%
Readers by discipline Count As %
Neuroscience 109 27%
Agricultural and Biological Sciences 76 19%
Biochemistry, Genetics and Molecular Biology 36 9%
Medicine and Dentistry 25 6%
Immunology and Microbiology 14 3%
Other 39 10%
Unknown 109 27%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 13. 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 31 March 2022.
All research outputs
#2,368,976
of 23,452,723 outputs
Outputs from Journal of Neuroinflammation
#332
of 2,712 outputs
Outputs of similar age
#31,724
of 265,610 outputs
Outputs of similar age from Journal of Neuroinflammation
#5
of 35 outputs
Altmetric has tracked 23,452,723 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,712 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one has done well, scoring higher than 87% 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 265,610 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 87% of its contemporaries.
We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.