Migraine causes recurrent and severe headaches and in some cases nausea, vomiting and photophobia. 80% of the cases are considered migraine without aura, and the remaining 20% are episodes in which the headache is preceded by transient neurological symptoms that are usually visual (migraine with aura).
Despite the high prevalence of this type of headache, “the majority of the genetic causes and pathophysiological mechanisms that are involved in it are still unknown, which makes finding effective treatments difficult,” says Xavier Gasull.
A new work published in the journal Neuron concludes that a mutation in the gene that codes for the ion channel TRESK —involved in the control of the excitability of neurons— causes the dysfunction of proteins that increase neuronal activity and induce migraines.
Experts Xavier Gasull and Alba Andrés-Bilbé from the Faculty of Medicine and Health Sciences, the Neurosciences Institute of the University of Barcelona ( UBNeuro ) and the Research Group in Neurophysiology at IDIBAPS participate in the study .
The control of neuronal excitability
Episodes of migraine are related to greater electrical excitability of sensory neurons. The electrical activity is controlled by proteins – the ion channels – that are responsible for facilitating or inhibiting the activation of neurons. The study, in particular, focuses on the ion channels TRESK and TREK, which are found in sensory neurons and slow down excessive neuronal activation.
According to the conclusions, a mutation in the gene that codes for the TRESK ion channel gives rise to a dysfunctional protein, which alters the ability of the channel to reduce electrical activity. Simultaneously, this mutation also generates another altered protein that affects the physiological function of other ion channels such as TREK1. The discovery of a mechanism by which a mutation generates two dysfunctional proteins – a process perhaps shared with other genetic pathologies – also opens up new perspectives that will have to be explored in the future.
“Paradoxically, other mutations that also eliminated the TRESK protein, but which did not cause migraine, have been described so far. In the new study, we verified that the combination of the two factors is necessary for a greater electrical activation of the sensory neurons, what causes the pain characteristic of migraine,” says Xavier Gasull.
The work, coordinated by the researcher Guillaume Sandoz, of the University of Nice and the National Center of Scientific Research of France (CNRS), will open new ways to design future therapeutic strategies against migraine, and it is a very significant advance to know in detail the mechanisms that cause episodes of migraine with aura, so far unknown.
Source: SINC
