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A Missense Mutation of the Gene Encoding Synaptic Vesicle Glycoprotein 2A (SV2A) Confers Seizure Susceptibility by Disrupting Amygdalar Synaptic GABA Release

Overview of attention for article published in Frontiers in Pharmacology, July 2016
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Title
A Missense Mutation of the Gene Encoding Synaptic Vesicle Glycoprotein 2A (SV2A) Confers Seizure Susceptibility by Disrupting Amygdalar Synaptic GABA Release
Published in
Frontiers in Pharmacology, July 2016
DOI 10.3389/fphar.2016.00210
Pubmed ID
Authors

Kentaro Tokudome, Takahiro Okumura, Ryo Terada, Saki Shimizu, Naofumi Kunisawa, Tomoji Mashimo, Tadao Serikawa, Masashi Sasa, Yukihiro Ohno

Abstract

Synaptic vesicle glycoprotein 2A (SV2A) is specifically expressed in the membranes of synaptic vesicles and modulates action potential-dependent neurotransmitter release. To explore the role of SV2A in the pathogenesis of epileptic disorders, we recently generated a novel rat model (Sv2a(L174Q) rat) carrying a missense mutation of the Sv2a gene and showed that the Sv2a(L174Q) rats were hypersensitive to kindling development (Tokudome et al., 2016). Here, we further conducted behavioral and neurochemical studies to clarify the pathophysiological mechanisms underlying the seizure vulnerability in Sv2a(L174Q) rats. Sv2a(L174Q) rats were highly susceptible to pentylenetetrazole (PTZ)-induced seizures, yielding a significantly higher seizure scores and seizure incidence than the control animals. Brain mapping analysis of Fos expression, a biological marker of neural excitation, revealed that the seizure threshold level of PTZ region-specifically elevated Fos expression in the amygdala in Sv2a(L174Q) rats. In vivo microdialysis study showed that the Sv2a(L174Q) mutation preferentially reduced high K(+) (depolarization)-evoked GABA release, but not glutamate release, in the amygdala. In addition, specific control of GABA release by SV2A was supported by its predominant expression in GABAergic neurons, which were co-stained with antibodies against SV2A and glutamate decarboxylase 1. The present results suggest that dysfunction of SV2A by the missense mutation elevates seizure susceptibility in rats by preferentially disrupting synaptic GABA release in the amygdala, illustrating the crucial role of amygdalar SV2A-GABAergic system in epileptogenesis.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 47 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 19%
Student > Bachelor 7 15%
Student > Ph. D. Student 4 9%
Student > Doctoral Student 3 6%
Student > Master 3 6%
Other 7 15%
Unknown 14 30%
Readers by discipline Count As %
Neuroscience 11 23%
Biochemistry, Genetics and Molecular Biology 6 13%
Medicine and Dentistry 6 13%
Agricultural and Biological Sciences 3 6%
Pharmacology, Toxicology and Pharmaceutical Science 3 6%
Other 2 4%
Unknown 16 34%
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 30 July 2016.
All research outputs
#18,465,988
of 22,880,691 outputs
Outputs from Frontiers in Pharmacology
#8,289
of 16,169 outputs
Outputs of similar age
#271,729
of 355,133 outputs
Outputs of similar age from Frontiers in Pharmacology
#64
of 134 outputs
Altmetric has tracked 22,880,691 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 16,169 research outputs from this source. They receive a mean Attention Score of 4.9. This one is in the 37th percentile – i.e., 37% 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 355,133 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 134 others from the same source and published within six weeks on either side of this one. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.