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Spatiotemporal progression of ubiquitin-proteasome system inhibition after status epilepticus suggests protective adaptation against hippocampal injury

Overview of attention for article published in Molecular Neurodegeneration, February 2017
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Title
Spatiotemporal progression of ubiquitin-proteasome system inhibition after status epilepticus suggests protective adaptation against hippocampal injury
Published in
Molecular Neurodegeneration, February 2017
DOI 10.1186/s13024-017-0163-2
Pubmed ID
Authors

Tobias Engel, Jaime Martinez-Villarreal, Christine Henke, Eva M. Jimenez-Mateos, Amaya Sanz-Rodriguez, Mariana Alves, Yasmina Hernandez-Santana, Gary P. Brennan, Aidan Kenny, Aoife Campbell, Jose J. Lucas, David C. Henshall

Abstract

The ubiquitin-proteasome-system (UPS) is the major intracellular pathway leading to the degradation of unwanted and/or misfolded soluble proteins. This includes proteins regulating cellular survival, synaptic plasticity and neurotransmitter signaling; processes controlling excitability thresholds that are altered by epileptogenic insults. Dysfunction of the UPS has been reported to occur in a brain region- and cell-specific manner and contribute to disease progression in acute and chronic brain diseases. Prolonged seizures, status epilepticus, may alter UPS function but there has been no systematic attempt to map when and where this occurs in vivo or to determine the consequences of proteasome inhibition on seizure-induced brain injury. To determine whether seizures lead to an impairment of the UPS, we used a mouse model of status epilepticus whereby seizures are triggered by an intra-amygdala injection of kainic acid. Status epilepticus in this model causes cell death in selected brain areas, in particular the ipsilateral CA3 subfield of the hippocampus, and the development of epilepsy after a short latent period. To monitor seizure-induced dysfunction of the UPS we used a UPS inhibition reporter mouse expressing the ubiquitin fusion degradation substrate ubiquitin(G76V)-green fluorescent protein. Treatment with the specific proteasome inhibitor epoxomicin was used to establish the impact of proteasome inhibition on seizure-induced pathology. Our studies show that status epilepticus induced by intra-amygdala kainic acid causes select spatio-temporal UPS inhibition which is most evident in damage-resistant regions of the hippocampus, including CA1 pyramidal and dentate granule neurons then appears later in astrocytes. In support of this exerting a beneficial effect, injection of mice with the proteasome inhibitor epoxomicin protected the normally vulnerable hippocampal CA3 subfield from seizure-induced neuronal death in the model. These studies reveal brain region- and cell-specific UPS impairment occurs after seizures and suggest UPS inhibition can protect against seizure-induced brain damage. Identifying networks or pathways regulated through the proteasome after seizures may yield novel target genes for the treatment of seizure-induced cell death and possibly epilepsy.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 2%
Unknown 43 98%

Demographic breakdown

Readers by professional status Count As %
Unspecified 7 16%
Student > Ph. D. Student 7 16%
Student > Bachelor 6 14%
Student > Master 3 7%
Student > Doctoral Student 2 5%
Other 8 18%
Unknown 11 25%
Readers by discipline Count As %
Neuroscience 9 20%
Unspecified 7 16%
Medicine and Dentistry 6 14%
Biochemistry, Genetics and Molecular Biology 5 11%
Business, Management and Accounting 1 2%
Other 5 11%
Unknown 11 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 08 March 2017.
All research outputs
#15,448,169
of 22,957,478 outputs
Outputs from Molecular Neurodegeneration
#720
of 852 outputs
Outputs of similar age
#198,083
of 311,668 outputs
Outputs of similar age from Molecular Neurodegeneration
#19
of 25 outputs
Altmetric has tracked 22,957,478 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 852 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.3. This one is in the 10th percentile – i.e., 10% 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 311,668 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 25 others from the same source and published within six weeks on either side of this one. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.