DIPARTIMENTO DI SCIENZE BIOMEDICHE
The aim of the research
The broad objective of our research project is to understand the mechanisms that cause familial hemiplegic migraine (FHM), a rare form of migraine with aura, characterized by attacks of usually throbbing unilateral often severe headache with associated symptoms such as photophobia, phonophobia, nausea; the headache is preceded by neurological aura symptoms, with visual, sensory, language disturbances and hemiparesis or motor weakness, that can be very prolonged and severe in some patients.
Since it is now clear that the primary cause of FHM (and of the more common forms of migraine) lies in the brain, but the cellular and circuit mechanisms of the primary brain dysfunction are unknown, our aim is to reveal these mechanisms using as animal models two different transgenic mice: one carries a FHM type 1 mutation in a protein that is essential for controlling neurotransmitter release at brain synapses, and the other carries a FHM type 2 mutation in a protein of astrocytes, that is important for clearing up the synapses from the neurotransmitters and the K+ ions released by neurons. We want to test the hypothesis that in both cases, the primary dysfunction is a deficient regulation of the dynamic equilibrium between cortical excitation and inhibition, that is essential for the proper processing of sensory stimuli by our brain and also to prevent the overexcitation that may cause the attack (by inducing a wave of depolarization across the cortex that activates the pain mechanisms causing the headache). Understanding the primary brain dysfunction in FHM is essential to be able to develop much needed more efficacious and specific drugs for preventive treatment and identify targets for new therapeutic tools.