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

Journal article (2017)

Authors

E Eising Leiden University Medical Center
R Shyti Leiden University Medical Center
Boukje de Vries Leiden University Medical Center
Arn M.J.M. van den Maagdenberg Leiden University Medical Center
Peter A.C. 't Hoen Leiden University Medical Center
L.S. Vijfhuizen Leiden University Medical Center
S.M.H. Huisman Leiden University Medical Center, Pattern Recognition and Bioinformatics - EEMCS
Ludo A. M. Broos Leiden University Medical Center
A.M.E.T.A. Mahfouz Leiden University Medical Center, Pattern Recognition and Bioinformatics - EEMCS
M.J.T. Reinders Pattern Recognition and Bioinformatics - EEMCS
MD Ferrari Leiden University Medical Center
EA Tolner Leiden University Medical Center
Research Group
Pattern Recognition and Bioinformatics (EEMCS) (TU Delft)
Copyright: © 2017 Else Eising, Reinald Shyti, Peter A.C. 't Hoen, L.S. Vijfhuizen, S.M.H. Huisman, Ludo A. M. Broos, A.M.E.T.A. Mahfouz, M.J.T. Reinders, Michel D. Ferrari, Else A. Tolner, Boukje de Vries, Arn M.J.M. van den Maagdenberg
DOI: https://doi.org/10.1007/s12035-015-9681-5
Migraine Familial hemiplegic migraine type 1 Gene expression profiling Deep serial analysis of gene expression Inflammation Interferon
More Info
expand_more

Published Date

2017

Language

English

Faculty

Electrical Engineering, Mathematics and Computer Science

Department

Intelligent Systems

Research Group

Pattern Recognition and Bioinformatics

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.