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Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis

Overview of attention for article published in Acta Neuropathologica Communications, November 2015
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  • Above-average Attention Score compared to outputs of the same age (62nd percentile)
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

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5 tweeters

Citations

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18 Dimensions

Readers on

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61 Mendeley
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Title
Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis
Published in
Acta Neuropathologica Communications, November 2015
DOI 10.1186/s40478-015-0255-6
Pubmed ID
Authors

Franziska Denk, Leanne M. Ramer, Erin L. K. S. Erskine, Mohammed A. Nassar, Yury Bogdanov, Massimo Signore, John N. Wood, Stephen B. McMahon, Matt S. Ramer

Abstract

Tamoxifen (TAM) is an important cancer therapeutic and an experimental tool for effecting genetic recombination using the inducible Cre-Lox technique. Despite its widespread use in the clinic and laboratory, we know little about its effects on the nervous system. This is of significant concern because TAM, via unknown mechanisms, induces cognitive impairment in humans. A hallmark of cellular stress is induction of Activating Transcription Factor 3 (Atf3), and so to determine whether TAM induces cellular stress in the adult nervous system, we generated a knock-in mouse in which Atf3 promoter activity drives transcription of TAM-dependent Cre recombinase (Cre-ERT2); when crossed with tdtomato reporter mice, Atf3 induction results in robust and permanent genetic labeling of cells in which it is up-regulated even transiently. We found that granular neurons of the olfactory bulb and dentate gyrus, vascular cells and ependymal cells throughout the brain, and peripheral sensory neurons expressed tdtomato in response to TAM treatment. We also show that TAM induced Atf3 up-regulation through inhibition of cholesterol epoxide hydrolase (ChEH): reporter expression was mitigated by delivery in vitamin E-rich wheat germ oil (vitamin E depletes ChEH substrates), and was partially mimicked by a ChEH-specific inhibitor. This work demonstrates that TAM stresses cells of the adult central and peripheral nervous systems and highlights concerns about clinical and experimental use of TAM. We propose TAM administration in vitamin E-rich vehicles such as wheat germ oil as a simple remedy.

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 61 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Unknown 60 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 19 31%
Researcher 10 16%
Student > Bachelor 8 13%
Professor > Associate Professor 4 7%
Student > Master 4 7%
Other 7 11%
Unknown 9 15%
Readers by discipline Count As %
Agricultural and Biological Sciences 16 26%
Neuroscience 12 20%
Biochemistry, Genetics and Molecular Biology 5 8%
Psychology 4 7%
Medicine and Dentistry 4 7%
Other 10 16%
Unknown 10 16%

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 24 June 2020.
All research outputs
#5,881,888
of 18,026,194 outputs
Outputs from Acta Neuropathologica Communications
#756
of 1,107 outputs
Outputs of similar age
#119,532
of 376,523 outputs
Outputs of similar age from Acta Neuropathologica Communications
#56
of 82 outputs
Altmetric has tracked 18,026,194 research outputs across all sources so far. This one is in the 47th percentile – i.e., 47% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,107 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.6. This one is in the 30th percentile – i.e., 30% 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 376,523 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 62% of its contemporaries.
We're also able to compare this research output to 82 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.