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Resetting the Stress System with a Mifepristone Challenge

Overview of attention for article published in Cellular and Molecular Neurobiology, September 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (71st percentile)
  • Above-average Attention Score compared to outputs of the same age and source (63rd percentile)

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Title
Resetting the Stress System with a Mifepristone Challenge
Published in
Cellular and Molecular Neurobiology, September 2018
DOI 10.1007/s10571-018-0614-5
Pubmed ID
Authors

Sergiu Dalm, Adriaan M. Karssen, Onno C. Meijer, Joseph K. Belanoff, E. Ronald de Kloet

Abstract

Psychotic depression is characterized by elevated circulating cortisol, and high daily doses of the glucocorticoid/progesterone antagonist mifepristone for 1 week are required for significant improvement. Using a rodent model, we find that such high doses of mifepristone are needed because the antagonist is rapidly degraded and poorly penetrates the blood-brain barrier, but seems to facilitate the entry of cortisol. We also report that in male C57BL/6J mice, after a 7-day treatment with a high dose of mifepristone, basal blood corticosterone levels were similar to that of vehicle controls. This is surprising because after the first mifepristone challenge, corticosterone remained elevated for about 16 h, and then decreased towards vehicle control levels at 24 h. At that time, stress-induced corticosterone levels of the 1xMIF were sevenfold higher than the 7xMIF group, the latter response being twofold lower than controls. The 1xMIF mice showed behavioral hyperactivity during exploration of the circular hole board, while the 7xMIF mice rather engaged in serial search patterns. To explain this rapid reset of corticosterone secretion upon recurrent mifepristone administration, we suggest the following: (i) A rebound glucocorticoid feedback after cessation of mifepristone treatment. (ii) Glucocorticoid agonism in transrepression and recruitment of cell-specific coregulator cocktails. (iii) A more prominent role of brain MR function in control of stress circuit activity. An overview table of neuroendocrine MIF effects is provided. The data are of interest for understanding the mechanistic underpinning of stress system reset as treatment strategy for stress-related diseases.

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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 12 19%
Student > Doctoral Student 7 11%
Other 7 11%
Researcher 7 11%
Student > Master 7 11%
Other 4 6%
Unknown 18 29%
Readers by discipline Count As %
Neuroscience 15 24%
Biochemistry, Genetics and Molecular Biology 8 13%
Agricultural and Biological Sciences 4 6%
Medicine and Dentistry 4 6%
Psychology 3 5%
Other 4 6%
Unknown 24 39%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 6. 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 28 September 2018.
All research outputs
#5,767,284
of 23,854,458 outputs
Outputs from Cellular and Molecular Neurobiology
#268
of 1,046 outputs
Outputs of similar age
#96,918
of 338,599 outputs
Outputs of similar age from Cellular and Molecular Neurobiology
#4
of 11 outputs
Altmetric has tracked 23,854,458 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,046 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one has gotten more attention than average, scoring higher than 74% 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 338,599 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 71% of its contemporaries.
We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.