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Single Ethanol Withdrawal Regulates Extrasynaptic δ-GABAA Receptors Via PKCδ Activation

Overview of attention for article published in Frontiers in Molecular Neuroscience, April 2018
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Title
Single Ethanol Withdrawal Regulates Extrasynaptic δ-GABAA Receptors Via PKCδ Activation
Published in
Frontiers in Molecular Neuroscience, April 2018
DOI 10.3389/fnmol.2018.00141
Pubmed ID
Authors

Juan Chen, Yang He, Yan Wu, Hang Zhou, Li-Da Su, Wei-Nan Li, Richard W. Olsen, Jing Liang, Yu-Dong Zhou, Yi Shen

Abstract

Alcohol (ethanol, EtOH) is one of the most widely abused drugs with profound effects on brain function and behavior. GABAA receptors (GABAARs) are one of the major targets for EtOH in the brain. Temporary plastic changes in GABAARs after withdrawal from a single EtOH exposure occur both in vivo and in vitro, which may be the basis for chronic EtOH addiction, tolerance and withdrawal symptoms. Extrasynaptic δ-GABAAR endocytosis is implicated in EtOH-induced GABAAR plasticity, but the mechanisms by which the relative abundance and localization of specific GABAARs are altered by EtOH exposure and withdrawal remain unclear. In this study, we investigated the mechanisms underlying rapid regulation of extrasynaptic δ-GABAAR by a single EtOH withdrawal in cultured rat hippocampal neurons. Thirty-minutes EtOH (60 mM) exposure increased extrasynaptic tonic current (Itonic) amplitude without affecting synaptic GABAAR function in neurons. In contrast, at 30 min after withdrawal, Itonic amplitude and responsiveness to acute EtOH were both reduced. Similar results occurred in neurons with okadaic acid (OA) or phorbol 12,13-dibutyrate (PDBu) exposure. Protein kinase C (PKC) inhibition prevented the reduction of Itonic amplitude and the tolerance to acute EtOH, as well as the reduction of GABAAR-δ subunit abundance induced by a single EtOH withdrawal. Moreover, EtOH withdrawal selectively increased PKCδ level, whereas PKCδ inhibition specifically rescued the EtOH-induced alterations in GABAAR-δ subunit level and δ-GABAAR function. Together, we provided strong evidence for the important roles of PKCδ in the rapid regulation of extrasynaptic δ-GABAAR induced by a single EtOH withdrawal.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 10 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 3 30%
Student > Ph. D. Student 2 20%
Student > Master 1 10%
Researcher 1 10%
Student > Postgraduate 1 10%
Other 0 0%
Unknown 2 20%
Readers by discipline Count As %
Medicine and Dentistry 2 20%
Agricultural and Biological Sciences 2 20%
Biochemistry, Genetics and Molecular Biology 1 10%
Computer Science 1 10%
Neuroscience 1 10%
Other 0 0%
Unknown 3 30%
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 03 May 2018.
All research outputs
#18,606,163
of 23,047,237 outputs
Outputs from Frontiers in Molecular Neuroscience
#2,294
of 2,919 outputs
Outputs of similar age
#253,413
of 326,650 outputs
Outputs of similar age from Frontiers in Molecular Neuroscience
#104
of 123 outputs
Altmetric has tracked 23,047,237 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,919 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 14th percentile – i.e., 14% of its peers scored the same or lower than it.
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We're also able to compare this research output to 123 others from the same source and published within six weeks on either side of this one. This one is in the 9th percentile – i.e., 9% of its contemporaries scored the same or lower than it.