The Antagonism of 5-HT6 Receptor Attenuates Current-Induced Spikes and Improves Long-Term Potentiation via the Regulation of M-Currents in a Pilocarpine-Induced Epilepsy Model

Recent studies have documented that reduced M-current promotes epileptogenesis and attenuates synaptic remodeling. Neurite growth is closely related to the level of 5-HT6 receptor (5-HT6R) in the central nervous system. However, little research is available regarding the relation between 5-HT6R and...

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Autores principales: Zhu, Chaofeng, Lin, Rong, Liu, Changyun, Huang, Mingzhu, Lin, Feng, Zhang, Gan, Zhang, Yuying, Miao, Junjie, Lin, Wanhui, Huang, Huapin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Pharmacology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212420/
https://www.ncbi.nlm.nih.gov/pubmed/32425770
http://dx.doi.org/10.3389/fphar.2020.00475
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author Zhu, Chaofeng
Lin, Rong
Liu, Changyun
Huang, Mingzhu
Lin, Feng
Zhang, Gan
Zhang, Yuying
Miao, Junjie
Lin, Wanhui
Huang, Huapin
author_facet Zhu, Chaofeng
Lin, Rong
Liu, Changyun
Huang, Mingzhu
Lin, Feng
Zhang, Gan
Zhang, Yuying
Miao, Junjie
Lin, Wanhui
Huang, Huapin
author_sort Zhu, Chaofeng
collection PubMed
description Recent studies have documented that reduced M-current promotes epileptogenesis and attenuates synaptic remodeling. Neurite growth is closely related to the level of 5-HT6 receptor (5-HT6R) in the central nervous system. However, little research is available regarding the relation between 5-HT6R and M-current and the role of 5-HT6R in M-current regulation. Herein, we found that the expression of 5-HT6R was notably increased and the expression of KNCQ2/3, the main components of the M channel, was decreased in a time-dependent manner in pilocarpine-induced chronic epileptic hippocampus. Interestingly, antagonism of 5-HT6R by SB271046 upregulated the expression of KCNQ2 but not KCNQ3. SB271046 greatly alleviated excitatory/inhibitory imbalance and improved the impaired LTP in the chronic epileptic hippocampus. Further mechanism exploration revealed that the above effects of SB271046 can be reversed by the M-channel inhibitor XE991, which also confirmed that SB271046 can indeed improve abnormal M current. These data indicate that the antagonism of 5-HT6R may decrease the excitability of hippocampal pyramidal neurons in chronic epileptic rats and improve the impaired long-term potentiation by upregulating the expression of KCNQ2 in the M-channel.
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spelling pubmed-72124202020-05-18 The Antagonism of 5-HT6 Receptor Attenuates Current-Induced Spikes and Improves Long-Term Potentiation via the Regulation of M-Currents in a Pilocarpine-Induced Epilepsy Model Zhu, Chaofeng Lin, Rong Liu, Changyun Huang, Mingzhu Lin, Feng Zhang, Gan Zhang, Yuying Miao, Junjie Lin, Wanhui Huang, Huapin Front Pharmacol Pharmacology Recent studies have documented that reduced M-current promotes epileptogenesis and attenuates synaptic remodeling. Neurite growth is closely related to the level of 5-HT6 receptor (5-HT6R) in the central nervous system. However, little research is available regarding the relation between 5-HT6R and M-current and the role of 5-HT6R in M-current regulation. Herein, we found that the expression of 5-HT6R was notably increased and the expression of KNCQ2/3, the main components of the M channel, was decreased in a time-dependent manner in pilocarpine-induced chronic epileptic hippocampus. Interestingly, antagonism of 5-HT6R by SB271046 upregulated the expression of KCNQ2 but not KCNQ3. SB271046 greatly alleviated excitatory/inhibitory imbalance and improved the impaired LTP in the chronic epileptic hippocampus. Further mechanism exploration revealed that the above effects of SB271046 can be reversed by the M-channel inhibitor XE991, which also confirmed that SB271046 can indeed improve abnormal M current. These data indicate that the antagonism of 5-HT6R may decrease the excitability of hippocampal pyramidal neurons in chronic epileptic rats and improve the impaired long-term potentiation by upregulating the expression of KCNQ2 in the M-channel. Frontiers Media S.A. 2020-04-28 /pmc/articles/PMC7212420/ /pubmed/32425770 http://dx.doi.org/10.3389/fphar.2020.00475 Text en Copyright © 2020 Zhu, Lin, Liu, Huang, Lin, Zhang, Zhang, Miao, Lin and Huang http://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
Zhu, Chaofeng
Lin, Rong
Liu, Changyun
Huang, Mingzhu
Lin, Feng
Zhang, Gan
Zhang, Yuying
Miao, Junjie
Lin, Wanhui
Huang, Huapin
The Antagonism of 5-HT6 Receptor Attenuates Current-Induced Spikes and Improves Long-Term Potentiation via the Regulation of M-Currents in a Pilocarpine-Induced Epilepsy Model
title The Antagonism of 5-HT6 Receptor Attenuates Current-Induced Spikes and Improves Long-Term Potentiation via the Regulation of M-Currents in a Pilocarpine-Induced Epilepsy Model
title_full The Antagonism of 5-HT6 Receptor Attenuates Current-Induced Spikes and Improves Long-Term Potentiation via the Regulation of M-Currents in a Pilocarpine-Induced Epilepsy Model
title_fullStr The Antagonism of 5-HT6 Receptor Attenuates Current-Induced Spikes and Improves Long-Term Potentiation via the Regulation of M-Currents in a Pilocarpine-Induced Epilepsy Model
title_full_unstemmed The Antagonism of 5-HT6 Receptor Attenuates Current-Induced Spikes and Improves Long-Term Potentiation via the Regulation of M-Currents in a Pilocarpine-Induced Epilepsy Model
title_short The Antagonism of 5-HT6 Receptor Attenuates Current-Induced Spikes and Improves Long-Term Potentiation via the Regulation of M-Currents in a Pilocarpine-Induced Epilepsy Model
title_sort antagonism of 5-ht6 receptor attenuates current-induced spikes and improves long-term potentiation via the regulation of m-currents in a pilocarpine-induced epilepsy model
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212420/
https://www.ncbi.nlm.nih.gov/pubmed/32425770
http://dx.doi.org/10.3389/fphar.2020.00475
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