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 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.

Else Eising, Reinald Shyti, Peter-Bram 't Hoen, Lisanne S. Vijfhuizen, Sjoerd Huisman, et al. Cortical spreading depression causes unique dysregulation of inflammatory pathways in a transgenic mouse model of migraine. Molecular Neurobiology, 54(4): pp. 2986–2996, 2017.
@article { bib:2017_molneuro_csd,
author = { Else Eising and Reinald Shyti and Peter-Bram 't Hoen and Lisanne S. Vijfhuizen and Sjoerd Huisman and Ludo A. M. Broos and Ahmed Mahfouz and Marcel Reinders and Michel D. Ferrari and Else A. Tolner and Boukje de Vries and Arn M. J. M. van den Maagdenberg },
title = { Cortical spreading depression causes unique dysregulation of inflammatory pathways in a transgenic mouse model of migraine },
journal = { Molecular Neurobiology },
volume = { 54 },
number = { 4 },
pages = { 2986 -- 2996 },
year = { 2017 },
doi = { 10.1007/s12035-015-9681-5 },
}
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