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Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures

Epilepsy is a relatively common condition, but more than 30% of patients have refractory epilepsy that is inadequately controlled by or is resistant to multiple drug treatments. Thus, new antiepileptic drugs based on newly identified mechanisms are required. A previous report revealed the suppressiv...

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Autores principales: Moriyama, Hiroshi, Nomura, Sadahiro, Imoto, Hirochika, Inoue, Takao, Fujiyama, Yuichi, Haji, Kohei, Maruta, Yuichi, Ishihara, Hideyuki, Suzuki, Michiyasu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517222/
https://www.ncbi.nlm.nih.gov/pubmed/34658898
http://dx.doi.org/10.3389/fphar.2021.766782
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author Moriyama, Hiroshi
Nomura, Sadahiro
Imoto, Hirochika
Inoue, Takao
Fujiyama, Yuichi
Haji, Kohei
Maruta, Yuichi
Ishihara, Hideyuki
Suzuki, Michiyasu
author_facet Moriyama, Hiroshi
Nomura, Sadahiro
Imoto, Hirochika
Inoue, Takao
Fujiyama, Yuichi
Haji, Kohei
Maruta, Yuichi
Ishihara, Hideyuki
Suzuki, Michiyasu
author_sort Moriyama, Hiroshi
collection PubMed
description Epilepsy is a relatively common condition, but more than 30% of patients have refractory epilepsy that is inadequately controlled by or is resistant to multiple drug treatments. Thus, new antiepileptic drugs based on newly identified mechanisms are required. A previous report revealed the suppressive effects of transient receptor potential melastatin 8 (TRPM8) activation on penicillin G-induced epileptiform discharges (EDs). However, it is unclear whether TRPM8 agonists suppress epileptic seizures or affect EDs or epileptic seizures in TRPM8 knockout (TRPM8KO) mice. We investigated the effects of TRPM8 agonist and lack of TRPM8 channels on EDs and epileptic seizures. Mice were injected with TRPM8 agonist 90 min after or 30 min before epilepsy-inducer injection, and electrocorticograms (ECoGs) were recorded under anesthesia, while behavior was monitored when awake. TRPM8 agonist suppressed EDs and epileptic seizures in wildtype (WT) mice, but not in TRPM8KO mice. In addition, TRPM8KO mice had a shorter firing latency of EDs, and EDs and epileptic seizures were deteriorated by the epilepsy inducer compared with those in WT mice, with the EDs being more easily propagated to the contralateral side. These findings suggest that TRPM8 activation in epileptic regions has anti-epileptic effects.
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spelling pubmed-85172222021-10-16 Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures Moriyama, Hiroshi Nomura, Sadahiro Imoto, Hirochika Inoue, Takao Fujiyama, Yuichi Haji, Kohei Maruta, Yuichi Ishihara, Hideyuki Suzuki, Michiyasu Front Pharmacol Pharmacology Epilepsy is a relatively common condition, but more than 30% of patients have refractory epilepsy that is inadequately controlled by or is resistant to multiple drug treatments. Thus, new antiepileptic drugs based on newly identified mechanisms are required. A previous report revealed the suppressive effects of transient receptor potential melastatin 8 (TRPM8) activation on penicillin G-induced epileptiform discharges (EDs). However, it is unclear whether TRPM8 agonists suppress epileptic seizures or affect EDs or epileptic seizures in TRPM8 knockout (TRPM8KO) mice. We investigated the effects of TRPM8 agonist and lack of TRPM8 channels on EDs and epileptic seizures. Mice were injected with TRPM8 agonist 90 min after or 30 min before epilepsy-inducer injection, and electrocorticograms (ECoGs) were recorded under anesthesia, while behavior was monitored when awake. TRPM8 agonist suppressed EDs and epileptic seizures in wildtype (WT) mice, but not in TRPM8KO mice. In addition, TRPM8KO mice had a shorter firing latency of EDs, and EDs and epileptic seizures were deteriorated by the epilepsy inducer compared with those in WT mice, with the EDs being more easily propagated to the contralateral side. These findings suggest that TRPM8 activation in epileptic regions has anti-epileptic effects. Frontiers Media S.A. 2021-10-01 /pmc/articles/PMC8517222/ /pubmed/34658898 http://dx.doi.org/10.3389/fphar.2021.766782 Text en Copyright © 2021 Moriyama, Nomura, Imoto, Inoue, Fujiyama, Haji, Maruta, Ishihara and Suzuki. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Moriyama, Hiroshi
Nomura, Sadahiro
Imoto, Hirochika
Inoue, Takao
Fujiyama, Yuichi
Haji, Kohei
Maruta, Yuichi
Ishihara, Hideyuki
Suzuki, Michiyasu
Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures
title Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures
title_full Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures
title_fullStr Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures
title_full_unstemmed Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures
title_short Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures
title_sort suppressive effects of transient receptor potential melastatin 8 agonist on epileptiform discharges and epileptic seizures
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517222/
https://www.ncbi.nlm.nih.gov/pubmed/34658898
http://dx.doi.org/10.3389/fphar.2021.766782
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