title: Transcriptomic Changes in Rat Cortex and Brainstem After Cortical Spreading Depression With or Without Pretreatment With Migraine Prophylactic Drugs.
abstract: Migraine with aura is a subtype of migraine characterized by transient neurological disturbances that usually precede headache. Cortical spreading depression (CSD) is the likely pathophysiological correlate of the aura phase of migraine, found in common and rare forms of migraine, such as familial hemiplegic migraine. CSD is a depolarization wave that propagates across the cerebral gray matter transiently suppressing neuronal activity. Prophylactic treatments for migraine, such as topiramate or valproate, reduce the number of CSD events. We evaluated changes in gene expression in rat cortex and brainstem after inducing CSD in the cortex, with and without a prophylactic treatment with topiramate or valproate. CSD induction showed similar transcriptomic profiles with and without treatment in cortex, involving genes related to hormone stimulus, apoptosis, synaptic transmission, and interleukin signaling. In brainstem, CSD with and without treatment, although to a lesser extent, also induced gene expression changes involving genes related to apoptosis. Half of the genes altered in brainstem after CSD were also differentially expressed in the same direction in cortex. No differences in gene expression were identified after CSD as a consequence of the treatments, neither in cortex nor in brainstem.
  
  
  
  Our results suggest that early after triggering the CSD, similar consequences are seen at the genetic level with or without prophylactic treatment. Gene expression changes induced by CSD in cortex and brainstem may help to better understand the underlying mechanisms and identify targets for therapeutic approaches.
authors.affiliation: Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain.
authors.forename: Cèlia
authors.initials: C
authors.lastname: Sintas
authors.affiliation: Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain; Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues, Barcelona, Catalonia, Spain.
authors.forename: Noèlia
authors.initials: N
authors.lastname: Fernàndez-Castillo
authors.affiliation: Pediatric Neurology Research Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Vila-Pueyo
authors.affiliation: Headache Research Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; Headache Unit, Neurology Department, Vall d'Hebron University Hospital, Barcelona, Catalonia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pozo-Rosich
authors.affiliation: Pediatric Neurology Research Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Macaya
authors.affiliation: Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain; Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues, Barcelona, Catalonia, Spain. Electronic address: bcormand@ub.edu.
authors.forename: Bru
authors.initials: B
authors.lastname: Cormand
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D053263:Gene Regulatory Networks / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D000077236:Topiramate; D059467:Transcriptome / Q000187:drug effects* / Q000502:physiology; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D012333:RNA, Messenger; D000077236:Topiramate; D005632:Fructose; D014635:Valproic Acid
keywords: Cortical spreading depression; migraine; topiramate; transcriptomics; valproate