title: Cortical Spreading Depression Causes Unique Dysregulation of Inflammatory Pathways in a Transgenic Mouse Model of Migraine.
abstract: Familial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of migraine with aura caused by mutations in CACNA1A that encodes the α1Asubunit of voltage-gated CaV2.1 calcium channels. Transgenic knock-in mice that carry the human FHM1 R192Q missense mutation ('FHM1 R192Q mice') exhibit an increased susceptibility to cortical spreading depression (CSD), the mechanism underlying migraine aura. Here, we analysed gene expression profiles from isolated cortical tissue of FHM1 R192Q mice 24 h after experimentally induced CSD in order to identify molecular pathways affected by CSD. Gene expression profiles were generated using deep serial analysis of gene expression sequencing. Our data reveal a signature of inflammatory signalling upon CSD in the cortex of both mutant and wild-type mice. However, only in the brains of FHM1 R192Q mice specific genes are up-regulated in response to CSD that are implicated in interferon-related inflammatory signalling. Our findings show that CSD modulates inflammatory processes in both wild-type and mutant brains, but that an additional unique inflammatory signature becomes expressed after CSD in a relevant mouse model of migraine.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Else
authors.initials: E
authors.lastname: Eising
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Reinald
authors.initials: R
authors.lastname: Shyti
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Peter A C
authors.initials: PAC
authors.lastname: 't Hoen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Lisanne S
authors.initials: LS
authors.lastname: Vijfhuizen
authors.affiliation: Department of Intelligent Systems, Faculty of EEMCS, Delft University of Technology, Delft, Netherlands.|Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Sjoerd M H
authors.initials: SMH
authors.lastname: Huisman
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ludo A M
authors.initials: LAM
authors.lastname: Broos
authors.affiliation: Department of Intelligent Systems, Faculty of EEMCS, Delft University of Technology, Delft, Netherlands.|Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mahfouz
authors.affiliation: Department of Intelligent Systems, Faculty of EEMCS, Delft University of Technology, Delft, Netherlands.
authors.forename: Marcel J T
authors.initials: MJT
authors.lastname: Reinders
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Michel D
authors.initials: MD
authors.lastname: Ferrari
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Else A
authors.initials: EA
authors.lastname: Tolner
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Boukje
authors.initials: B
authors.lastname: de Vries
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. A.M.J.M.van_den_Maagdenberg@lumc.nl.|Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. A.M.J.M.van_den_Maagdenberg@lumc.nl.
authors.forename: Arn M J M
authors.initials: AMJM
authors.lastname: van den Maagdenberg
mesh_terms: D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D016000:Cluster Analysis; D013181:Cortical Spreading Depression / Q000235:genetics*; D004195:Disease Models, Animal; D004843:Epistasis, Genetic; D063990:Gene Ontology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008881:Migraine Disorders / Q000150:complications* / Q000235:genetics / Q000503:physiopathology*; D060066:Protein Interaction Maps / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D014157:Transcription Factors
keywords: Deep serial analysis of gene expression; Familial hemiplegic migraine type 1; Gene expression profiling; Inflammation; Interferon; Migraine