Surprise, surprise, surprise: Hopkins scientists unexpectedly create epilep...( One of the brain's most important chemi...)

One of the brain's most important chemical messengers has led Johns Hopkins School of Medicine researchers on a wild ride. Primarily interested in how and why nerve cells die in neurodegenerative diseases like Lou Gerhig's disease, the scientists now find themselves with a new rat model of epilepsy, a disease characterized not by cell death, but by rapid and uncontrolled "firing" of brain cells.

Aware that extra amounts of the messenger can kill brain cells by over-stimulating them, the scientists thought preventing it from getting into cells might lead to cell death. But blocking one of the messenger's main transporters didn't kill nerve cells; instead, the rats developed epilepsy, complete with periods of staring and "freezing," the scientists report in the August 1 issue of the Journal of Neuroscience.

"We wanted to see how reducing transport of this messenger affected other brain chemicals and the brain itself, but we hadn't expected it to result in epilepsy," says Jeffrey Rothstein, M.D., Ph.D., professor of neurology and neuroscience at Johns Hopkins. "Now we need to track it down in people to see if the same mechanism is involved in the human condition."

Epilepsy has long been tied to reduced levels of a brain messenger called GABA, which dampens cells' likelihood of firing. However, the stimulating messenger the scientists study, called glutamate, had never been linked to epilepsy in animals or people.

Investigating further, the scientists discovered that the glutamate transporter they blocked imports glutamate molecules that are used by the cell to make new GABA molecules. The rats couldn't make new GABA, so over the course of 10 days, their GABA levels dropped and epileptic symptoms developed, says Rothstein.

"We've shown that the synthesis and release of GABA depends heavily on transporting glutamate into nerve cells," says Rothstein, also director of the Robert Packard Center for ALS Research at John
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
2-Aug-2002

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