↓ Skip to main content

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

Overview of attention for article published in Brain: A Journal of Neurology, January 2013
Altmetric Badge

About this Attention Score

  • Good Attention Score compared to outputs of the same age (70th percentile)
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

twitter
1 tweeter
patent
1 patent

Citations

dimensions_citation
52 Dimensions

Readers on

mendeley
28 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
CHOP regulates the p53–MDM2 axis and is required for neuronal survival after seizures
Published in
Brain: A Journal of Neurology, 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.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 28 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 21%
Researcher 6 21%
Student > Doctoral Student 6 21%
Professor > Associate Professor 3 11%
Student > Bachelor 3 11%
Other 4 14%
Readers by discipline Count As %
Agricultural and Biological Sciences 7 25%
Medicine and Dentistry 6 21%
Neuroscience 4 14%
Biochemistry, Genetics and Molecular Biology 3 11%
Psychology 3 11%
Other 5 18%

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
#3,186,576
of 11,700,978 outputs
Outputs from Brain: A Journal of Neurology
#2,441
of 4,663 outputs
Outputs of similar age
#88,227
of 304,690 outputs
Outputs of similar age from Brain: A Journal of Neurology
#34
of 71 outputs
Altmetric has tracked 11,700,978 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 4,663 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.8. This one is in the 46th percentile – i.e., 46% 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 304,690 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 70% of its contemporaries.
We're also able to compare this research output to 71 others from the same source and published within six weeks on either side of this one. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.