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Involvement of PPARγ in the Anticonvulsant Activity of EP-80317, a Ghrelin Receptor Antagonist

Overview of attention for article published in Frontiers in Pharmacology, September 2017
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Title
Involvement of PPARγ in the Anticonvulsant Activity of EP-80317, a Ghrelin Receptor Antagonist
Published in
Frontiers in Pharmacology, September 2017
DOI 10.3389/fphar.2017.00676
Pubmed ID
Authors

Chiara Lucchi, Anna M. Costa, Carmela Giordano, Giulia Curia, Marika Piat, Giuseppina Leo, Jonathan Vinet, Luc Brunel, Jean-Alain Fehrentz, Jean Martinez, Antonio Torsello, Giuseppe Biagini

Abstract

Ghrelin, des-acyl ghrelin and other related peptides possess anticonvulsant activities. Although ghrelin and cognate peptides were shown to physiologically regulate only the ghrelin receptor, some of them were pharmacologically proved to activate the peroxisome proliferator-activated receptor gamma (PPARγ) through stimulation of the scavenger receptor CD36 in macrophages. In our study, we challenged the hypothesis that PPARγ could be involved in the anticonvulsant effects of EP-80317, a ghrelin receptor antagonist. For this purpose, we used the PPARγ antagonist GW9662 to evaluate the modulation of EP-80317 anticonvulsant properties in two different models. Firstly, the anticonvulsant effects of EP-80317 were studied in rats treated with pilocarpine to induce status epilepticus (SE). Secondly, the anticonvulsant activity of EP-80317 was ascertained in the repeated 6-Hz corneal stimulation model in mice. Behavioral and video electrocorticographic (ECoG) analyses were performed in both models. We also characterized levels of immunoreactivity for PPARγ in the hippocampus of 6-Hz corneally stimulated mice. EP-80317 predictably antagonized seizures in both models. Pretreatment with GW9662 counteracted almost all EP-80317 effects both in mice and rats. Only the effects of EP-80317 on power spectra of ECoGs recorded during repeated 6-Hz corneal stimulation were practically unaffected by GW9662 administration. Moreover, GW9662 alone produced a decrease in the latency of tonic-clonic seizures and accelerated the onset of SE in rats. Finally, in the hippocampus of mice treated with EP-80317 we found increased levels of PPARγ immunoreactivity. Overall, these results support the hypothesis that PPARγ is able to modulate seizures and mediates the anticonvulsant effects of EP-80317.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 23 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 22%
Student > Ph. D. Student 4 17%
Other 3 13%
Professor > Associate Professor 2 9%
Student > Master 2 9%
Other 1 4%
Unknown 6 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 17%
Pharmacology, Toxicology and Pharmaceutical Science 3 13%
Neuroscience 3 13%
Immunology and Microbiology 2 9%
Agricultural and Biological Sciences 2 9%
Other 2 9%
Unknown 7 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 22 September 2017.
All research outputs
#20,448,386
of 23,003,906 outputs
Outputs from Frontiers in Pharmacology
#10,210
of 16,311 outputs
Outputs of similar age
#278,358
of 318,615 outputs
Outputs of similar age from Frontiers in Pharmacology
#162
of 275 outputs
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So far Altmetric has tracked 16,311 research outputs from this source. They receive a mean Attention Score of 5.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 275 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.