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Scientists have discovered tsunami-like waves in mice for the brain’s signaling molecule, which could explain the onset of migraine headaches with auras.
The results can help understand other brain conditions, such as stroke, epilepsy, and brain injury.
“Glutamate bars are a completely new mechanism for migraine headaches, and it’s a good bet that they play a role in other diseases of the nervous system,” said KS Brennan, a neurologist at the University of Utah.
Glutamate is a type of messenger molecule that stimulates nerve cells in the brain. This includes neurons, which send and receive brain signals, and astrocytes, which are specialized support cells that perform the task of cleaning the brain.
The new study found a massive influx of glutamate into the space between brain cells in mice, moving with changes in brain activity already known in people with migraines.
Understanding the causes of this terrible headache is the first step in finding new migraine treatments that can help more people relieve pain, nausea, and vomiting.
The role of glutamate in migraine headaches has been previously suggested. People with migraines have higher glutamate levels than people without migraines, either during or between migraine attacks.
Triggers also differ between people with migraines, but can include some foods and drinks, strong smells, bright lights, sun glare, stress, and fatigue.
In general, the root cause of migraine is not yet well understood, although there are some warning signs that a migraine is about to occur, throwing us back into auras, a phenomenon called diffusion depolarization, a sudden change in brain activity described as, “A wave of unbridled excitement” in the brain. It is believed to be the foundation of the migraine aura, however it also occurs in other brain conditions, such as stroke and other forms of brain seizures, which can be measured in people using electrodes.
It follows that overexcited brain cells may be related to one of the most excitable neurotransmitters in the brain, glutamate, but there is no direct evidence linking the two specifically in migraine.
The researchers studied glutamate signals in mice designed to mimic a rare subtype of migraine (with auras) that a person could inherit from their parents.
With some genetic modifications, the brain cells of these mice underwent their own glutamate transport processes. The researchers also used a binding protein that fluoresces when encountered with glutamate, allowing the team to visualize glutamate levels in the brains of these mice while they were awake.
In the brain images, “plumes” of fluorescent glutamate appeared, moving from a central starting point through the upper layers of the brain. On average, these bars lasted less than a second.
In theory, the increase in glutamate would trigger a chain reaction, in which the release of glutamate from a single neuron stimulates its neighbors to follow suit, which the researchers saw: a tsunami-like wave of fluorescent molecules when the glutamate invaded the brains of mice.
By measuring the frequency and duration of the glutamate waves, the researchers found that the problem was not only the neurons that were pumping so much glutamate, but the astrocytes were also too slow to clear the mess.
And when glutamate absorption was poor in healthy mice, glutamate columns also appeared in the images of their brains, indicating the mechanism of the game.
With further experiments, the researchers also showed that a wave of glutamate columns preceded the initiation of diffuse depolarization events produced by the chemicals, while preventing them from occurring by blocking the columns.
Of course, this study only included a small number of mice that were engineered to mimic one type of migraine, not people who experience migraines in different ways, with or without auras.
However, the work is beneficial because it points to a new molecular mechanism that supports unpleasant auras, a finding that, with more research, could translate, with more research, into a treatment to stop migraines and auras in their tracks. However, treatments that target the glutamate receptor have not always been effective.
Meanwhile, researchers are shifting their focus toward understanding how glutamate columns are implicated in other brain disorders, such as epilepsy and stroke, that exhibit similar waves of brain activity, according to ScienceAlert.
