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Epigenetic control of epilepsy target genes contributes to a cellular memory of epileptogenesis in cultured rat hippocampal neurons

Overview of attention for article published in Acta Neuropathologica Communications, October 2017
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Title
Epigenetic control of epilepsy target genes contributes to a cellular memory of epileptogenesis in cultured rat hippocampal neurons
Published in
Acta Neuropathologica Communications, October 2017
DOI 10.1186/s40478-017-0485-x
Pubmed ID
Authors

K. Kiese, J. Jablonski, J. Hackenbracht, J. K. Wrosch, T. W. Groemer, J. Kornhuber, I. Blümcke, K. Kobow

Abstract

Hypersynchronous neuronal excitation manifests clinically as seizure (ictogenesis), and may recur spontaneously and repetitively after a variable latency period (epileptogenesis). Despite tremendous research efforts to describe molecular pathways and signatures of epileptogenesis, molecular pathomechanisms leading to chronic epilepsy remain to be clarified. We hypothesized that epigenetic modifications may form the basis for a cellular memory of epileptogenesis, and used a primary neuronal cell culture model of the rat hippocampus to study the translation of massive neuronal excitation into persisting changes of epigenetic signatures and pro-epileptogenic target gene expression. Increased spontaneous activation of cultured neurons was detected 3 and 7 days after stimulation with 10 μM glutamate when compared to sham-treated time-matched controls using calcium-imaging in vitro. Chromatin-immunoprecipitation experiments revealed short-term (3 h, 7 h, and 24 h) and long-term (3 d and 2 weeks) changes in histone modifications, which were directly linked to decreased expression of two selected epilepsy target genes, e.g. excitatory glutamate receptor genes Gria2 and Grin2a. Increased promoter methylation observed 4 weeks after glutamate stimulation at respective genes suggested long-term repression of Gria2 and Grin2a genes. Inhibition of glutamatergic activation or blocking the propagation of action potentials in cultured neurons rescued altered gene expression and regulatory epigenetic modifications. Our data support the concept of a cellular memory of epileptogenesis and persisting epigenetic modifications of epilepsy target genes, which are able to turn normal into pro-epileptic neurons and circuits.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 32 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 22%
Student > Ph. D. Student 7 22%
Student > Master 6 19%
Student > Bachelor 5 16%
Student > Doctoral Student 1 3%
Other 1 3%
Unknown 5 16%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 25%
Neuroscience 7 22%
Biochemistry, Genetics and Molecular Biology 4 13%
Psychology 2 6%
Medicine and Dentistry 1 3%
Other 0 0%
Unknown 10 31%

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 11 July 2018.
All research outputs
#13,664,477
of 15,488,067 outputs
Outputs from Acta Neuropathologica Communications
#849
of 891 outputs
Outputs of similar age
#273,711
of 322,170 outputs
Outputs of similar age from Acta Neuropathologica Communications
#83
of 88 outputs
Altmetric has tracked 15,488,067 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 891 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.2. This one is in the 1st percentile – i.e., 1% 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 322,170 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 88 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.