TY - JOUR
T1 - Cortical Spreading Depression Causes Unique Dysregulation of Inflammatory Pathways in a Transgenic Mouse Model of Migraine
AU - Eising, Else
AU - Shyti, Reinald
AU - 't Hoen, Peter A.C.
AU - Vijfhuizen, Lisanne S.
AU - Huisman, Sjoerd M.H.
AU - Broos, Ludo A. M.
AU - Mahfouz, Ahmed
AU - Reinders, Marcel J.T.
AU - Ferrari, Michel D.
AU - Tolner, Else A.
AU - de Vries, Boukje
AU - van den Maagdenberg, Arn M.J.M.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Migraine
KW - Familial hemiplegic migraine type 1
KW - Gene expression profiling
KW - Deep serial analysis of gene expression
KW - Inflammation
KW - Interferon
UR - http://resolver.tudelft.nl/uuid:eeffef50-8828-4fc3-b4e8-89a51715a20c
U2 - 10.1007/s12035-015-9681-5
DO - 10.1007/s12035-015-9681-5
M3 - Article
SN - 0893-7648
VL - 54
SP - 2986
EP - 2996
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 4
ER -