Dl-3n-butylphthalide reduces epileptiform activity through GluA2-lacking calcium-permeable AMPARs in epilepsy models

Epilepsy is the most prevalent chronic neurological disorder, and its pathological mechanism indicates that an imbalance between excitatory and inhibitory neurotransmission leads to neuronal hyperexcitability. Previous studies have suggested that dl-3n-butylphthalide (NBP) regulates the excitatory n...

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Autores principales: Yang, Qin, Hu, Yi-Da, Wang, Xue-Feng, Zheng, Fang-Shuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716726/
https://www.ncbi.nlm.nih.gov/pubmed/29228686
http://dx.doi.org/10.18632/oncotarget.21529
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author Yang, Qin
Hu, Yi-Da
Wang, Xue-Feng
Zheng, Fang-Shuo
author_facet Yang, Qin
Hu, Yi-Da
Wang, Xue-Feng
Zheng, Fang-Shuo
author_sort Yang, Qin
collection PubMed
description Epilepsy is the most prevalent chronic neurological disorder, and its pathological mechanism indicates that an imbalance between excitatory and inhibitory neurotransmission leads to neuronal hyperexcitability. Previous studies have suggested that dl-3n-butylphthalide (NBP) regulates the excitatory neurotransmitter glutamate in the brains of epileptic mice, however, the mechanisms are unknown. We investigated behavioral and electrophysiological factors in rats using NBP. In an in vivo pentylenetetrazole (PTZ)-induced epileptic seizure animal model, NBP decreased the generalized tonic-clonic seizure (GTCS) severity. In an acute hippocampal slice 4-aminopyridine (4-AP) epilepsy model in vitro, NBP decreased the epileptiform activity and miniature excitatory postsynaptic current (mEPSC) amplitude; there was no change in the miniature inhibitory postsynaptic current (mIPSC) amplitude or frequency. This effect suggested changes in excitatory synaptic transmission, which was altered through postsynaptic GluA2-lacking calcium-permeable AMPA receptors (CP-AMPARs). These findings showed that NBP suppressed epileptiform activity in these epilepsy models and provided the first detailed electrophysiological analysis of the impact of NBP in epilepsy models, which may be employed in future experimental or clinical therapies for patients with epilepsy.
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spelling pubmed-57167262017-12-08 Dl-3n-butylphthalide reduces epileptiform activity through GluA2-lacking calcium-permeable AMPARs in epilepsy models Yang, Qin Hu, Yi-Da Wang, Xue-Feng Zheng, Fang-Shuo Oncotarget Research Paper Epilepsy is the most prevalent chronic neurological disorder, and its pathological mechanism indicates that an imbalance between excitatory and inhibitory neurotransmission leads to neuronal hyperexcitability. Previous studies have suggested that dl-3n-butylphthalide (NBP) regulates the excitatory neurotransmitter glutamate in the brains of epileptic mice, however, the mechanisms are unknown. We investigated behavioral and electrophysiological factors in rats using NBP. In an in vivo pentylenetetrazole (PTZ)-induced epileptic seizure animal model, NBP decreased the generalized tonic-clonic seizure (GTCS) severity. In an acute hippocampal slice 4-aminopyridine (4-AP) epilepsy model in vitro, NBP decreased the epileptiform activity and miniature excitatory postsynaptic current (mEPSC) amplitude; there was no change in the miniature inhibitory postsynaptic current (mIPSC) amplitude or frequency. This effect suggested changes in excitatory synaptic transmission, which was altered through postsynaptic GluA2-lacking calcium-permeable AMPA receptors (CP-AMPARs). These findings showed that NBP suppressed epileptiform activity in these epilepsy models and provided the first detailed electrophysiological analysis of the impact of NBP in epilepsy models, which may be employed in future experimental or clinical therapies for patients with epilepsy. Impact Journals LLC 2017-10-05 /pmc/articles/PMC5716726/ /pubmed/29228686 http://dx.doi.org/10.18632/oncotarget.21529 Text en Copyright: © 2017 Yang et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Yang, Qin
Hu, Yi-Da
Wang, Xue-Feng
Zheng, Fang-Shuo
Dl-3n-butylphthalide reduces epileptiform activity through GluA2-lacking calcium-permeable AMPARs in epilepsy models
title Dl-3n-butylphthalide reduces epileptiform activity through GluA2-lacking calcium-permeable AMPARs in epilepsy models
title_full Dl-3n-butylphthalide reduces epileptiform activity through GluA2-lacking calcium-permeable AMPARs in epilepsy models
title_fullStr Dl-3n-butylphthalide reduces epileptiform activity through GluA2-lacking calcium-permeable AMPARs in epilepsy models
title_full_unstemmed Dl-3n-butylphthalide reduces epileptiform activity through GluA2-lacking calcium-permeable AMPARs in epilepsy models
title_short Dl-3n-butylphthalide reduces epileptiform activity through GluA2-lacking calcium-permeable AMPARs in epilepsy models
title_sort dl-3n-butylphthalide reduces epileptiform activity through glua2-lacking calcium-permeable ampars in epilepsy models
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716726/
https://www.ncbi.nlm.nih.gov/pubmed/29228686
http://dx.doi.org/10.18632/oncotarget.21529
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