Cortical spreading depression causes unique dysregulation of inflammatory pathways in a transgenic mouse model of migraine
Eising, E., Shyti, R., 'T hoen, P. A. C., Vijfhuizen, L. S., Huisman, S. M. H., Broos, L. A. M., Mahfourz, A., Reinders, M. J. T., Ferrrari, M. D., Tolner, E. A., De Vries, B., & Van den Maagdenberg, A. M. J. M.
Cortical spreading depression causes unique dysregulation of inflammatory pathways in a transgenic mouse model of migraine. Molecular Biology, 54
(4), 2986-2996. doi:10.1007/s12035-015-9681-5.
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 voltagegated
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.