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Journal of Neuroscience

Article Metrics

Exacerbation of Epilepsy by Astrocyte Alkalization and Gap Junction Uncoupling

Overview of attention for article published in Journal of Neuroscience, January 2021
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Mentioned by

news
15 news outlets
blogs
2 blogs
twitter
39 tweeters

Readers on

mendeley
15 Mendeley
Title
Exacerbation of Epilepsy by Astrocyte Alkalization and Gap Junction Uncoupling
Published in
Journal of Neuroscience, January 2021
DOI 10.1523/jneurosci.2365-20.2020
Pubmed ID
Authors

Mariko Onodera, Jan Meyer, Kota Furukawa, Yuichi Hiraoka, Tomomi Aida, Kohichi Tanaka, Kenji F. Tanaka, Christine R. Rose, Ko Matsui

Abstract

Seizures invite seizures. At the initial stage of epilepsy, seizures intensify with each episode; however, the mechanisms underlying this exacerbation remain to be solved. Astrocytes have a strong control over neuronal excitability and the mode of information processing. This control is accomplished by adjusting the levels of various ions in the extracellular space. The network of astrocytes connected via gap junctions allows a wider or more confined distribution of these ions depending on the open probability of the gap junctions. K+ clearance relies on the K+ uptake by astrocytes and the subsequent diffusion of K+ through the astrocyte network. When astrocytes become uncoupled, K+ clearance becomes hindered. Accumulation of extracellular K+ leads to hyperexcitability of neurons. Here, using acute hippocampal slices from mice, we uncovered that brief periods of epileptiform activity result in gap junction uncoupling. In slices that experienced short-term epileptiform activity, extracellular K+ transients in response to glutamate became prolonged. Na+ imaging with a fluorescent indicator indicated that inter-cellular diffusion of small cations in the astrocytic syncytium via gap junctions became rapidly restricted after epileptiform activity. Using a transgenic mouse with astrocyte specific expression of a pH sensor (Lck-E2GFP), we confirmed that astrocytes react to epileptiform activity with intracellular alkalization. Application of a Na+/HCO3- co-transporter blocker led to suppression of intracellular alkalization of astrocytes and to the prevention of astrocyte uncoupling and hyperactivity intensification both in vitro and in vivo Therefore, inhibition of astrocyte alkalization could become a promising therapeutic strategy for countering epilepsy development.SIGNIFICANT STATEMENT We aimed to understand the mechanisms underlying the plastic change of forebrain circuits associated with the intensification of epilepsy. Here, we demonstrate that first-time exposure to only brief periods of epileptiform activity results in acute disturbance of the inter-cellular astrocyte network formed by gap junctions in hippocampal tissue slices from mice. Moreover, rapid clearance of K+ from the extracellular space was impaired. Epileptiform activity activated inward Na+/HCO3- co-transport in astrocytes by cell depolarization, resulting in their alkalization. Our data suggest that alkaline pH shifts in astrocytes lead to gap junction uncoupling, hampering K+ clearance, and thereby to exacerbation of epilepsy. Pharmacological intervention could become a promising new strategy to dampen neuronal hyperexcitability and epileptogenesis.

Twitter Demographics

The data shown below were collected from the profiles of 39 tweeters 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 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 15 100%

Demographic breakdown

Readers by professional status Count As %
Professor > Associate Professor 4 27%
Researcher 3 20%
Student > Ph. D. Student 3 20%
Student > Bachelor 2 13%
Professor 1 7%
Other 2 13%
Readers by discipline Count As %
Neuroscience 7 47%
Medicine and Dentistry 3 20%
Agricultural and Biological Sciences 2 13%
Computer Science 1 7%
Unspecified 1 7%
Other 0 0%
Unknown 1 7%

Attention Score in Context

This research output has an Altmetric Attention Score of 153. 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 24 March 2021.
All research outputs
#147,538
of 17,342,898 outputs
Outputs from Journal of Neuroscience
#208
of 20,983 outputs
Outputs of similar age
#5,052
of 320,351 outputs
Outputs of similar age from Journal of Neuroscience
#6
of 206 outputs
Altmetric has tracked 17,342,898 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 20,983 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.1. This one has done particularly well, scoring higher than 99% 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 320,351 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 206 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.