The study could open the way to treating various forms of acquired epilepsy and seizures that result from brain damage caused by trauma, infection, or tumors in the brain.
Since 1893, scientists have been aware of mysterious structures called perineural networks wrapped around neurons, but the function of these networks remained unknown. However, a group of scientists from the University of Virginia led by Harald Sontheimer (Harald Sontheimer) determined that these networks modulate electrical impulses in the brain. What's more, they found that seizures can occur when networks dissolve. The results of the work were published in the journal Nature Communications.
The researchers initially made this discovery in mice suffering from epilepsy caused by a fatal brain cancer called glioblastoma, the first symptom of which is often seizures. Glioblastoma is the only cancer that can grow in space. Because the skull blocks the cancer from expanding outward, the tumor produces an excessive amount of an excitatory chemical neurotransmitter (glutamate) that kills nearby healthy cells to make room for growth.
In addition to glutamate, the tumor secretes an enzyme that destroys the surrounding extracellular matrix, a gel-like substance that holds brain cells in place. Glioblastomas are highly cancerous and are known to be able to spread in the body. The secreted enzyme is a kind of knife that cuts the cancer cells, allowing them to move freely.
To their surprise, scientists also observed how the enzyme attacks the perineuronal networks wrapped around GABA-inhibiting neurons (Gamma-aminobutyric acid), which help prevent seizures.
Italian neuroscientist Camillo Golgi first discovered perineuronal networks in 1893, but then he misunderstood their function. Golgi called the networks a "corset" and said that they most likely interfered with the exchange of messages between neurons. Sontheimer's study refutes this. The scientist, on the other hand, discovered that networks support messaging. Neurons covered by perineuronal meshes have a lower membrane capacity and the ability to store an electrical charge, which means they can fire a pulse and recharge up to two times faster than non-networked neurons.
When they suddenly lose their perineural networks, the results can be catastrophic: by applying this enzyme to a brain without a tumor, scientists saw that the very enzymatic degradation of perineural networks was enough to provoke seizures - even when the neurons remained intact.
Researchers are now focusing their attention on how perineural networks may play in other forms of acquired epilepsy - for example, from head trauma or brain infection - that will move them closer to creating an effective drug.
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“We've solved the 125-year-old mystery of neurology! That's what basic science is - keeping an open and observant mind and answering old and new questions,”says Sontheimer.
According to the World Health Organization, more than 50 million people worldwide suffer from epilepsy, a third of whom are not susceptible to known antiepileptic treatments.
Dmitry Mazalevsky