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CHOP regulates the p53–MDM2 axis and is required for neuronal survival after seizures

Overview of attention for article published in Brain, January 2013
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  • Average Attention Score compared to outputs of the same age and source

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Title
CHOP regulates the p53–MDM2 axis and is required for neuronal survival after seizures
Published in
Brain, January 2013
DOI 10.1093/brain/aws337
Pubmed ID
Authors

Tobias Engel, Amaya Sanz-Rodgriguez, Eva M. Jimenez-Mateos, Caoimhin G. Concannon, Alba Jimenez-Pacheco, Catherine Moran, Guillaume Mesuret, Emilie Petit, Norman Delanty, Michael A. Farrell, Donncha F. O’Brien, Jochen H. M. Prehn, Jose J. Lucas, David C. Henshall

Abstract

Hippocampal sclerosis is a frequent pathological finding in patients with temporal lobe epilepsy and can be caused by prolonged single or repeated brief seizures. Both DNA damage and endoplasmic reticulum stress have been implicated as underlying molecular mechanisms in seizure-induced brain injury. The CCAAT/enhancer-binding protein homologous protein (CHOP) is a transcriptional regulator induced downstream of DNA damage and endoplasmic reticulum stress, which can promote or inhibit apoptosis according to context. Recent work has proposed inhibition of CHOP as a suitable neuroprotective strategy. Here, we show that transcript and protein levels of CHOP increase in surviving subfields of the hippocampus after prolonged seizures (status epilepticus) in mouse models. CHOP was also elevated in the hippocampus from epileptic mice and patients with pharmacoresistant epilepsy. The hippocampus of CHOP-deficient mice was much more vulnerable to damage in mouse models of status epilepticus. Moreover, compared with wild-type animals, CHOP-deficient mice subject to status epilepticus developed more spontaneous seizures, displayed protracted hippocampal neurodegeneration and a deficit in a hippocampus-dependent object-place recognition task. The absence of CHOP was associated with a supra-maximal induction of p53 after status epilepticus, and inhibition of p53 abolished the cell death-promoting consequences of CHOP deficiency. The protective effect of CHOP could be partly explained by activating transcription of murine double minute 2 that targets p53 for degradation. These data demonstrate that CHOP is required for neuronal survival after seizures and caution against inhibition of CHOP as a neuroprotective strategy where excitotoxicity is an underlying pathomechanism.

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The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 47 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 23%
Researcher 8 17%
Student > Bachelor 8 17%
Student > Doctoral Student 7 15%
Professor > Associate Professor 3 6%
Other 8 17%
Unknown 2 4%
Readers by discipline Count As %
Medicine and Dentistry 9 19%
Agricultural and Biological Sciences 7 15%
Biochemistry, Genetics and Molecular Biology 7 15%
Neuroscience 7 15%
Psychology 3 6%
Other 10 21%
Unknown 4 9%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 05 September 2017.
All research outputs
#8,262,445
of 25,374,917 outputs
Outputs from Brain
#5,026
of 7,626 outputs
Outputs of similar age
#85,260
of 290,753 outputs
Outputs of similar age from Brain
#48
of 95 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one has received more attention than most of these and is in the 66th percentile.
So far Altmetric has tracked 7,626 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.7. This one is in the 33rd percentile – i.e., 33% 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 290,753 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 69% of its contemporaries.
We're also able to compare this research output to 95 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.