SALT LAKE CITY, Utah — Migraines appear to result from surges in a brain chemical commonly used in processed food, according to new research. Experiments on mice found that an abnormal release of glutamate in spaces between neurons spark a tsunami-like wave of activity. Huge plumes of glutamate flood gray matter, setting off blinding headaches that blight the lives of over 36 million Americans, according to the American Migraine Foundation.
Migraines are classified by the World Health Organization as among the most disabling illnesses. They lead to more sick days than any other. Women are three times more prone – perhaps because of changing levels in the sex hormone estrogen. The severe, long-lasting headaches affect 12 percent of people. Some can have a warning visual disturbance, called an aura. Many sufferers have nausea and sensitivity to light.
Glutamate is an essential neurotransmitter that helps cells communicate. Too much can damage them, so the brain has evolved ways to limit its effects. Glutamate’s salty component monosodium glutamate (MSG) has flavored and preserved meaty and savory products for decades. Drugs targeting it could nip migraines in the bud.
The phenomenon could also lead to better therapies for other conditions, including stroke and head injury.
“This is something new under the sun. Glutamate plumes are a completely new mechanism of migraine, and it’s a good bet they are players in other diseases of the nervous system,” says co-corresponding author Dr. K.C. Brennan, a University of Utah Health professor of neurology, in a statement.
‘What the heck was that?’
Lead-author Patrick Parker, a graduate student at the University of Utah, stumbled on the discovery by chance. He was studying abnormalities in glutamate signaling in rodents carrying a human gene that leads to a form of the condition that runs in families. Known as FHM2, the gene mutation slows the rate of glutamate removal from the brain, sending neurons into overdrive. However, surprisingly, large puffs of glutamate appeared spontaneously and seemed to spread from a central location.
“Everything I’d read about neural glutamate signaling told me the plumes shouldn’t be there,” says Parker. “It wasn’t exactly a ‘eureka’ moment. More like, ‘What the heck was that?'”
Deeper analysis tracked the “chemical cascade” to a dysfunctional interaction between neurons and astrocytes, specialized cells that control glutamate levels. Either too much glutamate or too few astrocytes could lead to plumes.
“The common denominator is an imbalance between release and reuptake and an excess of glutamate in the extracellular space,” explains Brennan.
Plumes tied to more than just migraines
The study suggests migraines are caused by a chain reaction in which a nerve cell fires massively. It releases large amounts of glutamate and other substances that charge up neighboring neurons and then those next to them, and so on. The waves, called “spreading depolarizations,” sweep the brain like a ripple in a pond – or a tsunami caused by an earthquake.
Unlike seizures, another devastating brain event, they are just as common. In a stroke, brain hemorrhage, and traumatic brain injury, the waves can be just as damaging. The plumes predicted their onset and could be prevented.
“This shows plumes don’t just coincide with spreading depolarizations. They are involved in their generation,” says Parker.
Notably, the team saw plumes both in mice engineered to carry the human FHM2 gene and normal control animals. This means plumes are likely to be relevant well beyond migraine, where spreading depolarizations underlie the aura and trigger headache.
“There is an emerging theme of impaired control of glutamate by various means in migraine – and plumes add compellingly to that story,” says Parker.
Still no definite link between MSG and poor health
The researchers now want to directly test if glutamate plumes are involved in other neurological disorders. It could lead to the development of better therapies for multiple diseases.
“We have our work cut out for us, but when Mother Nature throws you this kind of curveball, you have to follow up on it,” says Brennan.
Most of the fear around MSG dates back to a mouse study from 1969. It found very high doses cause brain damage and impair newborns’ growth. MSG is a common item in Asian cuisine. It’s the main ingredient in soy sauce.
Many people have reported suffering headaches or migraine attacks after consuming MSG. Still, there have been no scientific studies into the alleged link. Food authorities have labeled it safe, despite controversy over its long-term effects.
The study is published in the journal Neuron.
SWNS writer Mark Waghorn contributed to this report.