Scientists discover gene linked to a common form of migraine

September 26, 2010

Montreal, September 26th, 2010 at 1:00 PM - An international study led by scientists at Université de Montréal and University of Oxford, has identified a gene associated with common migraines. Their findings show that a mutation in the KCNK18 gene inhibits the function of a protein called TRESK. TRESK normally plays a key role in nerve cell communication. Published today in Nature Medicine, this study may have implications for people who suffer from recurrent headaches, which include more than six million Canadians.

Previously, genes for migraine have been found only in a rare form involving headaches combined with limb weakness limited to one side of the body. "We focused on the more common types of migraine, without this muscle weakness, in our study, and looked at genes controlling brain excitability," says lead author Ron Lafreniere, Associate Director of the Centre of Excellence in Neuromics of the Université de Montréal (CENUM).

The researchers compared the DNA from migraine sufferers to that of non-sufferers. "We found a mutation in the KCNK18 gene that interrupts TRESK function in one large family suffering from migraine with aura," say Lafreniere. "When we tested everyone in the family, all those who suffered from migraine also had the mutation."

Aura migraines are those that are preceded or accompanied by sensory warning symptoms or signs (auras), such as flashes of light, blind spots or tingling in an arm or leg. The ensuing headache can be associated with sensitivity to lights, sounds, and smells, as well as nausea and occasional vomiting.

Mutation results in incomplete TRESK protein

The mutation causes production of an incomplete form of TRESK which disrupt the normal functioning of this protein. The end result is an alteration in the electrical activity (excitability) of cells. "We now have direct evidence that migraine is a nerve excitability problem and have highlighted a key causal pathway in migraine' says the joint lead author, Dr Zameel Cader from the MRC Functional Genomics Unit at Oxford.

TRESK present in migraine-relevant areas

Cell culture and in vitro experiments revealed that TRESK is present in certain neurons of the brain. "We showed that TRESK is in specific neuronal structures (trigeminal ganglia and dorsal root ganglia) that have been linked to migraine and pain pathways," says Lafreniere.

"This is a highly significant finding because activation of trigeminal ganglion neurons is central to migraine development and increased activation of these neurons could very plausibly increase the risk for developing a migraine attack," explains senior author Guy Rouleau, a Université de Montréal professor and Director of the Sainte-Justine University Hospital Research Center. "While TRESK mutations are present only in a small number of migraine sufferers, because we believe that TRESK helps control the excitability of nerve cells, our results suggest that increasing TRESK activity pharmacologically may help reduce the frequency or severity of migraine episodes, irrespective of their origin."
About migraines

Migraines are debilitating chronic headaches that can cause pain for hours or days. They can begin in the early teen years and may be triggered by many things, including stress, odors, certain foods, alcohol, etc.

Partners in research:

This study was funded by Genome Canada, Génome Québec, Emerillon Therapeutics, the Wellcome Trust, Pfizer, the Medical Research Council (UK) and the Natural Sciences and Engineering Research Council of Canada.

On the Web: Media contact:

Sophie Langlois
Director, Media Relations
Telephone: 514 343 7704

University of Montreal

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to