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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-8517222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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