Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization
Por:
Vila-Pueyo M, Cuenca-León E, Queirós AC, Kulis M, Sintas C, Cormand B, Martín-Subero JI, Pozo-Rosich P, Fernandez-Castillo N and Macaya A
Publicada:
1 feb 2023
Resumen:
BackgroundCortical 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. ObjectiveTo investigate whether cortical spreading depolarization with and without chronic treatment with topiramate or valproate affect the DNA methylation of the cortex. MethodsSprague-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. ResultsThe 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. ConclusionsOur results may provide insights into the underlying physiological mechanisms of migraine with aura and emphasize the role of epigenetics in migraine susceptibility.
Filiaciones:
Vila-Pueyo M:
Headache and Neurological Pain Research Group, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain
Pediatric Neurology Research Group, Vall Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain
Cuenca-León E:
Headache and Neurological Pain Research Group, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Spain
Queirós AC:
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Spain
Kulis M:
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Spain
Sintas C:
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Spain
Cormand B:
Centro de Investigación Biomédica en Red de Enfermedades Raras, Spain
Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Spain
Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain
Martín-Subero JI:
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Spain
Instituciò Catalana de Recerca i Estudis Avancats, Barcelona, Spain
Pozo-Rosich P:
Headache and Neurological Pain Research Group, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain
Headache Unit, Neurology Department, Vall d'Hebron University Hospital, Barcelona, Spain
Fernandez-Castillo N:
Centro de Investigación Biomédica en Red de Enfermedades Raras, Spain
Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Spain
Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain
Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain
Macaya A:
Pediatric Neurology Research Group, Vall Hebron Institute of Research, Universitat Autònoma de Barcelona, Spain
Institute of Neuroscience, Universitat Autònoma de Barcelona, Barcelona Spain
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