Abstract | Migraine: from genes to models and mechanisms

Migraine is a common neurovascular brain disorder that is characterized by recurrent attacks of severe headache and neurological symptoms that include nausea, vomiting and hypersensitivity to sound, smell and light. Main migraine subtypes are distinguished based on the presence of an aura that is characterized as a wave of glial and neuronal depolarization that proceeds through the cortex and is thought to activate headache mechanisms, at least in those patients that also experience an aura. There is debate to what extent neuronal and vascular mechanisms are primarily involved in migraine pathophysiology. Using our transgenic mouse models that carry mutations previously identified in migraine we aim to dissect the underlying disease mechanisms, not only of migraine but also of the co-morbidities, such as epilepsy and stroke. We take advantage of the fact that similar clinical features are also seen with monogenic forms of migraine, e.g. Familial Hemiplegic Migraine (FHM) and Retinal Vasculopathy with Cerebral Encephalopathy with Systemic manifestations (RVCL-S), for which we have identified causal genes. Our research also involves genome-wide association studies, performed within our International Headache Genetics Consortium, to identify genetic factors in the polygenic forms of migraine and, more recently, started the use of human iPSCs to generate human cellular models.