Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization

Background: Cortical spreading depolarization, the cause of migraine aura, is a short-lasting depolarization wave that moves across the brain cortex, transiently suppressing neuronal activity. Prophylactic treatments for migraine, such as topiramate or valproate, reduce the number of cortical spread...

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Autores: Vila-Pueyo, Marta, Cuenca León, Ester, Queirós, Ana C., Kulis, Marta, Sintas Vives, Cèlia, Cormand Rifà, Bru, Martín-Subero, José Ignacio, Pozo-Rosich, Patricia, Fernàndez Castillo, Noèlia, Macaya Ruiz, Alfons
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2023
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/197784
Acceso en línea:https://hdl.handle.net/2445/197784
Access Level:acceso abierto
Palabra clave:Models animals en la investigació
Epigenètica
Migranya
Animal models in research
Epigenetics
Migraine
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spelling Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarizationVila-Pueyo, MartaCuenca León, EsterQueirós, Ana C.Kulis, MartaSintas Vives, CèliaCormand Rifà, BruMartín-Subero, José IgnacioPozo-Rosich, PatriciaFernàndez Castillo, NoèliaMacaya Ruiz, AlfonsModels animals en la investigacióEpigenèticaMigranyaAnimal models in researchEpigeneticsMigraineBackground: Cortical spreading depolarization, the cause of migraine aura, is a short-lasting depolarization wave that moves across the brain cortex, transiently suppressing neuronal activity. Prophylactic treatments for migraine, such as topiramate or valproate, reduce the number of cortical spreading depression events in rodents. Objective: To investigate whether cortical spreading depolarization with and without chronic treatment with topiramate or valproate affect the DNA methylation of the cortex. Methods: Sprague-Dawley rats were intraperitoneally injected with saline, topiramate or valproate for four weeks when cortical spreading depolarization were induced and genome-wide DNA methylation was performed in the cortex of six rats per group. Results: The DNA methylation profile of the cortex was significantly modified after cortical spreading depolarization, with and without topiramate or valproate. Interestingly, topiramate reduced by almost 50% the number of differentially methylated regions, whereas valproate increased them by 17%, when comparing to the non-treated group after cortical spreading depolarization induction. The majority of the differentially methylated regions lay within intragenic regions, and the analyses of functional group over-representation retrieved several enriched functions, including functions related to protein processing in the cortical spreading depolarization without treatment group; functions related to metabolic processes in the cortical spreading depolarization with topiramate group; and functions related to synapse and ErbB, MAPK or retrograde endocannabinoid signaling in the cortical spreading depolarization with valproate group. Conclusions: Our results may provide insights into the underlying physiological mechanisms of migraine with aura and emphasize the role of epigenetics in migraine susceptibility.SAGE Publications2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/197784Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1177/03331024221146317Cephalalgia, 2023, vol. 43, num. 2, p. 333102422114631https://doi.org/10.1177/03331024221146317(c) International Headache Society, 2023info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1977842026-05-27T06:46:51Z
dc.title.none.fl_str_mv Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization
title Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization
spellingShingle Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization
Vila-Pueyo, Marta
Models animals en la investigació
Epigenètica
Migranya
Animal models in research
Epigenetics
Migraine
title_short Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization
title_full Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization
title_fullStr Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization
title_full_unstemmed Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization
title_sort Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization
dc.creator.none.fl_str_mv Vila-Pueyo, Marta
Cuenca León, Ester
Queirós, Ana C.
Kulis, Marta
Sintas Vives, Cèlia
Cormand Rifà, Bru
Martín-Subero, José Ignacio
Pozo-Rosich, Patricia
Fernàndez Castillo, Noèlia
Macaya Ruiz, Alfons
author Vila-Pueyo, Marta
author_facet Vila-Pueyo, Marta
Cuenca León, Ester
Queirós, Ana C.
Kulis, Marta
Sintas Vives, Cèlia
Cormand Rifà, Bru
Martín-Subero, José Ignacio
Pozo-Rosich, Patricia
Fernàndez Castillo, Noèlia
Macaya Ruiz, Alfons
author_role author
author2 Cuenca León, Ester
Queirós, Ana C.
Kulis, Marta
Sintas Vives, Cèlia
Cormand Rifà, Bru
Martín-Subero, José Ignacio
Pozo-Rosich, Patricia
Fernàndez Castillo, Noèlia
Macaya Ruiz, Alfons
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Models animals en la investigació
Epigenètica
Migranya
Animal models in research
Epigenetics
Migraine
topic Models animals en la investigació
Epigenètica
Migranya
Animal models in research
Epigenetics
Migraine
description Background: Cortical spreading depolarization, the cause of migraine aura, is a short-lasting depolarization wave that moves across the brain cortex, transiently suppressing neuronal activity. Prophylactic treatments for migraine, such as topiramate or valproate, reduce the number of cortical spreading depression events in rodents. Objective: To investigate whether cortical spreading depolarization with and without chronic treatment with topiramate or valproate affect the DNA methylation of the cortex. Methods: Sprague-Dawley rats were intraperitoneally injected with saline, topiramate or valproate for four weeks when cortical spreading depolarization were induced and genome-wide DNA methylation was performed in the cortex of six rats per group. Results: The DNA methylation profile of the cortex was significantly modified after cortical spreading depolarization, with and without topiramate or valproate. Interestingly, topiramate reduced by almost 50% the number of differentially methylated regions, whereas valproate increased them by 17%, when comparing to the non-treated group after cortical spreading depolarization induction. The majority of the differentially methylated regions lay within intragenic regions, and the analyses of functional group over-representation retrieved several enriched functions, including functions related to protein processing in the cortical spreading depolarization without treatment group; functions related to metabolic processes in the cortical spreading depolarization with topiramate group; and functions related to synapse and ErbB, MAPK or retrograde endocannabinoid signaling in the cortical spreading depolarization with valproate group. Conclusions: Our results may provide insights into the underlying physiological mechanisms of migraine with aura and emphasize the role of epigenetics in migraine susceptibility.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/197784
url https://hdl.handle.net/2445/197784
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1177/03331024221146317
Cephalalgia, 2023, vol. 43, num. 2, p. 333102422114631
https://doi.org/10.1177/03331024221146317
dc.rights.none.fl_str_mv (c) International Headache Society, 2023
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) International Headache Society, 2023
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv SAGE Publications
publisher.none.fl_str_mv SAGE Publications
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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