Cortical Spreading Depression Causes Unique Dysregulation of Inflammatory Pathways in a Transgenic Mouse Model of Migraine

Else Eising, Reinald Shyti, Peter A.C. 't Hoen, Lisanne S. Vijfhuizen, Sjoerd M.H. Huisman, Ludo A. M. Broos, Ahmed Mahfouz, Marcel J.T. Reinders, Michel D. Ferrari, Else A. Tolner, Boukje de Vries, Arn M.J.M. van den Maagdenberg

Research output: Contribution to journalArticleScientificpeer-review

30 Citations (Scopus)
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Abstract

Familial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of migraine with aura caused by mutations in CACNA1A that encodes the α1A subunit 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.
Original languageEnglish
Pages (from-to)2986-2996
Number of pages11
JournalMolecular Neurobiology
Volume54
Issue number4
DOIs
Publication statusPublished - 2017

Keywords

  • Migraine
  • Familial hemiplegic migraine type 1
  • Gene expression profiling
  • Deep serial analysis of gene expression
  • Inflammation
  • Interferon

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