Development of epilepsy: key role for astrocytes


A study, published in Nature Medicine found that star-shaped brain cells that are often overlooked by doctors and researchers as mere support cells appear to play a key role in the development of epilepsy.

It's one of the first times scientists have produced firm evidence implicating the cells, known as astrocytes, in a common human disease.

Researchers found that astrocytes can serve as ground zero in the brain, setting off a harmful cascade of electrical activity in the brain by sending out a brain chemical that triggers other brain cells to fire out of control.

" This opens up a new vista in efforts to treat epilepsy. It might be possible to treat epilepsy not by depressing or slowing brain function, as many of the current medications do, but by targeting brain cells that have been completely overlooked," says Maiken Nedergaard, of Center for Aging and Developmental Biology, who led the research.

" The main function of astrocytes is to maintain a healthy environment for neurons," says Nedergaard. " The electrical signaling in the brain is so sophisticated that it's crucial that the environment be optimal. When the astrocytes start acting abnormally, it's easy to see how serious disease might result."

Last year she showed that astrocytes magnify the damage to neurons after spinal cord injury. And currently she's looking at their role in Alzheimer's disease.

Nedergaard notes that in epilepsy, researchers have long known that an early sign of the disease in the brain are abnormal cells called reactive astrocytes – over-sized, bloated, star-shaped cells that no longer function properly. " People have thought that reactive astrocytes were caused by epilepsy, not that they could be the cause."

In the study, Nedergaard and colleagues showed that astrocytes actually generate seizure activity, and the team linked astrocytes to a brain chemical long known to be a key player in the development of epilepsy.
They showed that glutamate, which hypes up neurons and can make them fire uncontrollably, is released by astrocytes and can trigger seizure-like activity in the brain.

Then the team tested medications currently used to treat the disease. Epilepsy describes a condition in the brain where neurons start firing wildly and uncontrollably, sometimes resulting in seizures, and most medications aim to reduce such firing. The team showed that agents like Gabapentin and Valproate reduced the type of chemical signaling that causes astrocytes to release glutamate.

According to Nedergaard, many researchers have thought that epilepsy occurs when neurons that normally inhibit or slow down other neurons lose their power, as if the brakes on a speeding car were faulty. Current medications are aimed at making those molecular "brakes" more powerful and reining signals back in. But such drugs have side effects like drowsiness. Her work opens up a new avenue to understand the disease.

" The potential role of astrocytes in the generation of epilepsy has been largely ignored," says Michel Berg, of the Strong Epilepsy Center. " Epilepsy involves a re-organization of the brain's pathways, in a way that is not completely understood, that results in recurrent seizures. Currently we have drugs to treat seizures, but not to prevent the whole process.”

More than 2 million Americans have epilepsy. Current medications stop seizures in about two-thirds of patients, but others often struggle for years or even a lifetime to cope with symptoms including seizures. Surgery to remove a small amount of troublesome brain tissue is often successful in such cases. The disease can come about as a result of a brain injury or because of genetic abnormalities in the way the brain develops.

Source: University of Rochester Medical Center, 2005


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