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Enrichment of Circular RNA Expression Deregulation at the Transition to Recurrent Spontaneous Seizures in Experimental Temporal Lobe Epilepsy

Mesial temporal lobe epilepsy (mTLE) is a common form of epilepsy and is characterized by recurrent spontaneous seizures originating from the temporal lobe. The majority of mTLE patients develop pharmacoresistance to available anti-epileptic drugs (AEDs) while exhibiting severe pathological changes...

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Autores principales: Gomes-Duarte, Andreia, Bauer, Sebastian, Venø, Morten T., Norwood, Braxton A., Henshall, David C., Kjems, Jørgen, Rosenow, Felix, Vangoor, Vamshidhar R., Pasterkamp, R. Jeroen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876452/
https://www.ncbi.nlm.nih.gov/pubmed/33584828
http://dx.doi.org/10.3389/fgene.2021.627907
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author Gomes-Duarte, Andreia
Bauer, Sebastian
Venø, Morten T.
Norwood, Braxton A.
Henshall, David C.
Kjems, Jørgen
Rosenow, Felix
Vangoor, Vamshidhar R.
Pasterkamp, R. Jeroen
author_facet Gomes-Duarte, Andreia
Bauer, Sebastian
Venø, Morten T.
Norwood, Braxton A.
Henshall, David C.
Kjems, Jørgen
Rosenow, Felix
Vangoor, Vamshidhar R.
Pasterkamp, R. Jeroen
author_sort Gomes-Duarte, Andreia
collection PubMed
description Mesial temporal lobe epilepsy (mTLE) is a common form of epilepsy and is characterized by recurrent spontaneous seizures originating from the temporal lobe. The majority of mTLE patients develop pharmacoresistance to available anti-epileptic drugs (AEDs) while exhibiting severe pathological changes that can include hippocampal atrophy, neuronal death, gliosis and chronic seizures. The molecular mechanisms leading to mTLE remain incompletely understood, but are known to include defects in post-transcriptional gene expression regulation, including in non-coding RNAs (ncRNAs). Circular RNAs (circRNAs) are a class of recently rediscovered ncRNAs with high levels of expression in the brain and proposed roles in diverse neuronal processes. To explore a potential role for circRNAs in epilepsy, RNA-sequencing (RNA-seq) was performed on hippocampal tissue from a rat perforant pathway stimulation (PPS) model of TLE at different post-stimulation time points. This analysis revealed 218 differentially expressed (DE) circRNAs. Remarkably, the majority of these circRNAs were changed at the time of the occurrence of the first spontaneous seizure (DOFS). The expression pattern of two circRNAs, circ_Arhgap4 and circ_Nav3, was further validated and linked to miR-6328 and miR-10b-3p target regulation, respectively. This is the first study to examine the regulation of circRNAs during the development of epilepsy. It reveals an intriguing link between circRNA deregulation and the transition of brain networks into the state of spontaneous seizure activity. Together, our results provide a molecular framework for further understanding the role and mechanism-of-action of circRNAs in TLE.
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spelling pubmed-78764522021-02-12 Enrichment of Circular RNA Expression Deregulation at the Transition to Recurrent Spontaneous Seizures in Experimental Temporal Lobe Epilepsy Gomes-Duarte, Andreia Bauer, Sebastian Venø, Morten T. Norwood, Braxton A. Henshall, David C. Kjems, Jørgen Rosenow, Felix Vangoor, Vamshidhar R. Pasterkamp, R. Jeroen Front Genet Genetics Mesial temporal lobe epilepsy (mTLE) is a common form of epilepsy and is characterized by recurrent spontaneous seizures originating from the temporal lobe. The majority of mTLE patients develop pharmacoresistance to available anti-epileptic drugs (AEDs) while exhibiting severe pathological changes that can include hippocampal atrophy, neuronal death, gliosis and chronic seizures. The molecular mechanisms leading to mTLE remain incompletely understood, but are known to include defects in post-transcriptional gene expression regulation, including in non-coding RNAs (ncRNAs). Circular RNAs (circRNAs) are a class of recently rediscovered ncRNAs with high levels of expression in the brain and proposed roles in diverse neuronal processes. To explore a potential role for circRNAs in epilepsy, RNA-sequencing (RNA-seq) was performed on hippocampal tissue from a rat perforant pathway stimulation (PPS) model of TLE at different post-stimulation time points. This analysis revealed 218 differentially expressed (DE) circRNAs. Remarkably, the majority of these circRNAs were changed at the time of the occurrence of the first spontaneous seizure (DOFS). The expression pattern of two circRNAs, circ_Arhgap4 and circ_Nav3, was further validated and linked to miR-6328 and miR-10b-3p target regulation, respectively. This is the first study to examine the regulation of circRNAs during the development of epilepsy. It reveals an intriguing link between circRNA deregulation and the transition of brain networks into the state of spontaneous seizure activity. Together, our results provide a molecular framework for further understanding the role and mechanism-of-action of circRNAs in TLE. Frontiers Media S.A. 2021-01-28 /pmc/articles/PMC7876452/ /pubmed/33584828 http://dx.doi.org/10.3389/fgene.2021.627907 Text en Copyright © 2021 Gomes-Duarte, Bauer, Venø, Norwood, Henshall, Kjems, Rosenow, Vangoor and Pasterkamp. 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 Genetics
Gomes-Duarte, Andreia
Bauer, Sebastian
Venø, Morten T.
Norwood, Braxton A.
Henshall, David C.
Kjems, Jørgen
Rosenow, Felix
Vangoor, Vamshidhar R.
Pasterkamp, R. Jeroen
Enrichment of Circular RNA Expression Deregulation at the Transition to Recurrent Spontaneous Seizures in Experimental Temporal Lobe Epilepsy
title Enrichment of Circular RNA Expression Deregulation at the Transition to Recurrent Spontaneous Seizures in Experimental Temporal Lobe Epilepsy
title_full Enrichment of Circular RNA Expression Deregulation at the Transition to Recurrent Spontaneous Seizures in Experimental Temporal Lobe Epilepsy
title_fullStr Enrichment of Circular RNA Expression Deregulation at the Transition to Recurrent Spontaneous Seizures in Experimental Temporal Lobe Epilepsy
title_full_unstemmed Enrichment of Circular RNA Expression Deregulation at the Transition to Recurrent Spontaneous Seizures in Experimental Temporal Lobe Epilepsy
title_short Enrichment of Circular RNA Expression Deregulation at the Transition to Recurrent Spontaneous Seizures in Experimental Temporal Lobe Epilepsy
title_sort enrichment of circular rna expression deregulation at the transition to recurrent spontaneous seizures in experimental temporal lobe epilepsy
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876452/
https://www.ncbi.nlm.nih.gov/pubmed/33584828
http://dx.doi.org/10.3389/fgene.2021.627907
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