The research in this thesis was aimed at identifying genes and molecular pathways involved in migraine. To this end, two gene expression analyses were performed in brain tissue obtained from... Show moreThe research in this thesis was aimed at identifying genes and molecular pathways involved in migraine. To this end, two gene expression analyses were performed in brain tissue obtained from transgenic mouse models for familial hemiplegic migraine (FHM), a monogenic subtype of migraine with aura. Next, a study was conducted aimed at analyzing epigenetic marks at migraine candidate genes in FHM mice. In addition to the studies in migraine-relevant mouse models, the genetic architecture of migraine was explored by performing various gene-based pathway analyses to mine the extensive data sets resulting from genome wide association studies (GWAS) for the common forms of migraine. With these data, the overlap in genetic architecture of migraine with aura (MA) and migraine without aura (MO) was explored, as well as the cell types and brain regions that are likely involved in the pathophysiology of migraine and the two migraine subtypes. Finally, a gene expression profiling study was performed in blood of patients suffering from primary headache, in this case cluster headache. Combining the various approaches let to the identification of migraine-relevant genes, pathways and cell types that helps to unravel pathophysiological mechanisms of migraine and other primary headache disorders. Show less
Eising, E.; Pelzer, N.; Vijfhuizen, L.S.; Vries, B. de; Ferrari, M.D.; Hoen, P.A.C. 't; ... ; Maagdenberg, A.M.J.M. van den 2017
Familial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of migraine with aura caused by mutations in CACNA1A that encodes the alpha(1A) subunit of voltage-gated Ca(V)2.1 calcium... Show moreFamilial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of migraine with aura caused by mutations in CACNA1A that encodes the alpha(1A) subunit of voltage-gated Ca(V)2.1 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. Show less
Eising, E.; Leeuw, C. de; Min, J.L.; Anttila, V.; Verheijen, M.H.G.; Terwindt, G.M.; ... ; Int Headache Genetics Consortium 2016
