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Changes in excitatory and inhibitory receptor expression and network activity during induction and establishment of epilepsy in the rat Reduced Intensity Status Epilepticus (RISE) model

The RISE model is an effective system to study the underlying molecular and cellular mechanisms involved in the initiation and maintenance of epilepsy in vivo. Here we profiled the expression of excitatory and inhibitory neurotransmitter receptor subunits and synaptic scaffolding proteins in the hip...

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Autores principales: Needs, Hope I., Henley, Benjamin S., Cavallo, Damiana, Gurung, Sonam, Modebadze, Tamara, Woodhall, Gavin, Henley, Jeremy M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pergamon Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892273/
https://www.ncbi.nlm.nih.gov/pubmed/31356824
http://dx.doi.org/10.1016/j.neuropharm.2019.107728
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author Needs, Hope I.
Henley, Benjamin S.
Cavallo, Damiana
Gurung, Sonam
Modebadze, Tamara
Woodhall, Gavin
Henley, Jeremy M.
author_facet Needs, Hope I.
Henley, Benjamin S.
Cavallo, Damiana
Gurung, Sonam
Modebadze, Tamara
Woodhall, Gavin
Henley, Jeremy M.
author_sort Needs, Hope I.
collection PubMed
description The RISE model is an effective system to study the underlying molecular and cellular mechanisms involved in the initiation and maintenance of epilepsy in vivo. Here we profiled the expression of excitatory and inhibitory neurotransmitter receptor subunits and synaptic scaffolding proteins in the hippocampus and temporal lobe and compared these changes with alterations in network activity at specific timepoints during epileptogenesis. Significant changes occurred in all of the ionotropic glutamate receptor subunits tested during epilepsy induction and progression and the profile of these changes differed between the hippocampus and temporal lobe. Notably, AMPAR subunits were dramatically decreased during the latent phase of epilepsy induction, matched by a profound decrease in the network response to kainate application in the hippocampus. Moreover, decreases in the GABA(A)β3 subunit are consistent with a loss of inhibitory input contributing to the perturbation of excitatory/inhibitory balance and seizure generation. These data highlight the synaptic reorganisation that mediates the relative hypoexcitability prior to the manifestation of seizures and subsequent hyperexcitability when spontaneous seizures develop. These patterns of changes give new insight into the mechanisms underpinning epilepsy and provide a platform for future investigations targeting particular receptor subunits to reduce or prevent seizures.
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spelling pubmed-68922732019-12-16 Changes in excitatory and inhibitory receptor expression and network activity during induction and establishment of epilepsy in the rat Reduced Intensity Status Epilepticus (RISE) model Needs, Hope I. Henley, Benjamin S. Cavallo, Damiana Gurung, Sonam Modebadze, Tamara Woodhall, Gavin Henley, Jeremy M. Neuropharmacology Article The RISE model is an effective system to study the underlying molecular and cellular mechanisms involved in the initiation and maintenance of epilepsy in vivo. Here we profiled the expression of excitatory and inhibitory neurotransmitter receptor subunits and synaptic scaffolding proteins in the hippocampus and temporal lobe and compared these changes with alterations in network activity at specific timepoints during epileptogenesis. Significant changes occurred in all of the ionotropic glutamate receptor subunits tested during epilepsy induction and progression and the profile of these changes differed between the hippocampus and temporal lobe. Notably, AMPAR subunits were dramatically decreased during the latent phase of epilepsy induction, matched by a profound decrease in the network response to kainate application in the hippocampus. Moreover, decreases in the GABA(A)β3 subunit are consistent with a loss of inhibitory input contributing to the perturbation of excitatory/inhibitory balance and seizure generation. These data highlight the synaptic reorganisation that mediates the relative hypoexcitability prior to the manifestation of seizures and subsequent hyperexcitability when spontaneous seizures develop. These patterns of changes give new insight into the mechanisms underpinning epilepsy and provide a platform for future investigations targeting particular receptor subunits to reduce or prevent seizures. Pergamon Press 2019-11-01 /pmc/articles/PMC6892273/ /pubmed/31356824 http://dx.doi.org/10.1016/j.neuropharm.2019.107728 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Needs, Hope I.
Henley, Benjamin S.
Cavallo, Damiana
Gurung, Sonam
Modebadze, Tamara
Woodhall, Gavin
Henley, Jeremy M.
Changes in excitatory and inhibitory receptor expression and network activity during induction and establishment of epilepsy in the rat Reduced Intensity Status Epilepticus (RISE) model
title Changes in excitatory and inhibitory receptor expression and network activity during induction and establishment of epilepsy in the rat Reduced Intensity Status Epilepticus (RISE) model
title_full Changes in excitatory and inhibitory receptor expression and network activity during induction and establishment of epilepsy in the rat Reduced Intensity Status Epilepticus (RISE) model
title_fullStr Changes in excitatory and inhibitory receptor expression and network activity during induction and establishment of epilepsy in the rat Reduced Intensity Status Epilepticus (RISE) model
title_full_unstemmed Changes in excitatory and inhibitory receptor expression and network activity during induction and establishment of epilepsy in the rat Reduced Intensity Status Epilepticus (RISE) model
title_short Changes in excitatory and inhibitory receptor expression and network activity during induction and establishment of epilepsy in the rat Reduced Intensity Status Epilepticus (RISE) model
title_sort changes in excitatory and inhibitory receptor expression and network activity during induction and establishment of epilepsy in the rat reduced intensity status epilepticus (rise) model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892273/
https://www.ncbi.nlm.nih.gov/pubmed/31356824
http://dx.doi.org/10.1016/j.neuropharm.2019.107728
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